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| # | nctid | status | why_stop | label | phase | diseases | icdcodes | drugs | smiless | criteria |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | NCT03704714 | suspended | protocol being amended for stats/accrual changes as per pi | 0 | phase 1/phase 2 | ['aggressive non-hodgkin lymphoma', 'b-cell non-hodgkin lymphoma', 'cd20 positive', 'diffuse large b-cell lymphoma unclassifiable', 'intravascular large b-cell lymphoma', 'primary mediastinal (thymic) large b-cell lymphoma', 't-cell/histiocyte-rich large b-cell lymphoma', 'transformed follicular lymphoma to diffuse large b-cell lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['E70.321', 'Z17.0', 'Z67.10', 'Z67.20', 'Z67.30', 'Z67.40', 'Z67.90']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['cyclophosphamide', 'doxorubicin hydrochloride', 'prednisone', 'vincristine sulfate'] | ['C1CNP(=O)(OC1)N(CCCl)CCCl', 'CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O.Cl', 'CC12CC(=O)C3C(C1CCC2(C(=O)CO)O)CCC4=CC(=O)C=CC34C', 'CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O.OS(=O)(=O)O'] | Inclusion Criteria: - Patient must have a confirmed diagnosis of: - De novo DLBCL including the clinical subtypes of primary mediastinal, - cell/histiocyte-rich large B-cell lymphoma and intravascular DLBCL OR - De novo transformed DLBCL from follicular lymphoma (FL) OR - Any high grade CD20+ B-cell lymphoma per World Health Organization (WHO) 2016 OR - CD20+ aggressive B-cell lymphoma unclassifiable. - Patient must be deemed an appropriate candidate for R-CHOP therapy. - Patients must be naive to prior therapy for the study diagnosis. - Patient must have advanced stage III/IV early stage disease where provider determines single modality therapy with chemo-immunotherapy is most appropriate (i.e radiation deferred). - Patient must have measurable disease (defined as >= 1.5 cm in diameter) with correlated fludeoxyglucose F-18 (FDG)-avidity on positron emission tomography (PET) scan with Deauville score of 4 or 5 at time of diagnosis. - Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2. - Absolute neutrophil count (ANC) >= 1000/mm^3, independent of growth factor support or >= 500/mm^3 in cases of ongoing bone marrow involvement (in either case, these must be independent of transfusion support) documented =< 28 days prior to registration. - Platelets >= 100,000/mm^3, or >= 50,000 in cases of ongoing bone marrow involvement (In either case, these must be independent of transfusion support) documented =< 28 days prior to registration. - Total bilirubin =< 1.5 x upper limit of normal (ULN) documented =< 28 days prior to registration. - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 3 x ULN documented =< 28 days prior to registration. - Creatinine clearance >= 25 mL/min documented =< 28 days prior to registration. - Females of child-bearing potential (FOCBP) and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period. - NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: - Has not undergone a hysterectomy or bilateral oophorectomy. - Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months). - Females of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 7 days prior to registration on study. - Patients must have the ability to understand and willingness to sign a written informed consent prior to registration on study. Exclusion Criteria: - Patients who have received prior therapy intended to treat the study diagnosis are not eligible. - Patients who have received prior anti-PD-1/L1 therapy for any indication are not eligible. - Patients who require urgent cytoreductive therapy (e.g. surgery or radiation) are not eligible. - Subjects with known immunodeficiency, known autoimmune disease, or concurrent use of immunomodulatory agents are not eligible. - Patients who have a condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications =< 14 days prior to registration are not eligible. - NOTE: Inhaled steroids and adrenal replacement steroid doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted. - Patients with known central nervous system (CNS) involvement are not eligible. - Patients with an active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy are not eligible. - NOTE: Exceptions to this are as follows: localized non-melanotic skin cancer and any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment. Prostate and breast cancer patients undergoing hormone therapy with no currently active disease are eligible. - Patients with known human immunodeficiency virus (HIV) are not eligible. - Patients with clinically active hepatitis A, B, or C infections are not eligible. - NOTE: Patients with a history of hepatitis may be eligible if they have a normal titer. Such cases should be approved by the study principal investigator (PI). - Patients who have any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator?s opinion, could compromise the subject?s safety or put the study outcomes at risk are not eligible. - Pregnant or nursing females are not eligible. - Patients with uncontrolled intercurrent illness including, but not limited to, any of the following are not eligible: - Ongoing or active systemic infection. - Symptomatic congestive heart failure. - Myocardial infarction within 6 months prior to registration. - Unstable angina pectoris. - Uncontrolled or symptomatic cardiac arrhythmias. - Any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional classification. - Psychiatric illness/social situations that would limit compliance with study requirements. |
| 2 | NCT02573012 | completed | 1 | phase 4 | ['rheumatoid arthritis'] | ["['M06.9', 'M05.9', 'M06.08', 'M06.00', 'M06.011', 'M06.012', 'M06.019']"] | ['placebo matched to prednisone', 'prednisone'] | ['CC12CC(=O)C3C(C1CCC2(C(=O)CO)O)CCC4=CC(=O)C=CC34C'] | Inclusion Criteria: Tocilizumab-experienced participants: - Comply with the requirements of the study protocol (including treatment on an outpatient basis) - Rheumatoid arthritis (RA) of greater than or equal to (>=) 6 months duration diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria or 2010 ACR / European League Against Rheumatism (EULAR) criteria - Have received tocilizumab either subcutaneous (162 milligram [mg] once in a week) or intravenously (8 milligram per kilogram [mg/kg] once every 4 weeks) for the treatment of RA for at least 24 weeks prior to randomization - Have received 5 - 15 milligrams per day [mg/day] of glucocorticoids (prednisone or equivalent) for the treatment of RA for at least 20 weeks prior to screening - Currently receiving 5 mg/day of prednisone - Have attained and maintained LDA (DAS28 ESR score <=3.2) or remission (DAS28 ESR score less than [<] 2.6) for at least 4 weeks prior to randomization Tocilizumab-naïve participants: - Comply with the requirements of the study protocol (including treatment on an outpatient basis) - RA of >=6 months duration diagnosed according to the revised 1987 ACR criteria or 2010 ACR / EULAR criteria - Have active RA (defined as DAS28 ESR score greater than [>] 3.2) - Are considered by the investigator as inadequate responders to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs) - Are receiving 5 - 15 mg/day prednisone (or equivalent) for the treatment of RA Exclusion Criteria: General - Major surgery (including joint surgery) within 8 weeks prior to screening, or planned major surgery during the study and up to 6 months after randomization - Pregnant women or nursing (breastfeeding) mothers - In females of childbearing potential, a positive serum pregnancy test at screening - Females of childbearing potential unwilling or unable to use a reliable means of contraception (for example, physical barrier [participant or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during study treatment and for a minimum of 3 months after the last dose of tocilizumab - Body weight of >=150 kilogram (kg) - Lack of peripheral venous access Disease-related - RA of functional Class 4, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis - Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (for example, vasculitis, pulmonary fibrosis, or Felty syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the investigator - Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 years - Prior or current inflammatory joint disease other than RA (for example, gout, Lyme disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic arthritis, arthropathy of inflammatory bowel disease), or prior or current joint infections - Previous history of primary or secondary adrenal insufficiency Previous or Concomitant Prohibited Therapy - Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening - Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD20) - Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of screening - Intraarticular (IA) or parenteral glucocorticoids for the treatment of RA within 4 weeks prior to screening - Previous treatment with glucocorticoids for conditions other than RA, at any dose and in any formulation used continuously for >1 week, during the last 1 year prior to screening. Topical glucocorticoid creams or ointments for the treatment of skin conditions (for example eczema) are allowed - Immunization with a live/attenuated vaccine within 30 days prior to screening. Participants must agree not to take live attenuated vaccines (including seasonal nasal flu vaccine, varicella vaccine for shingles or chickenpox, vaccines for measles, mumps or rubella without or with varicella [MMR or MMRV], oral polio vaccine and vaccines for yellow fever), within 30 days before the Screening Visit, throughout the duration of the trial and for 60 days following the last dose of study drug - Any previous treatment with alkylating agents such as chlorambucil or with total lymphoid irradiation Laboratory Exclusion Criteria - Inadequate haematological, renal and liver function - Positive hepatitis B surface antigen or hepatitis C antibody Previous or Concomitant Conditions - History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies - Evidence of current serious uncontrolled cardiovascular (including uncontrolled hyperlipidemia), nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal (GI) disease - Current liver disease as determined by the investigator - History of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions that might predispose to perforations - Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other opportunistic infections (including, but not limited to, tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, Epstein-Barr virus, cytomegalovirus and herpes zoster, but excluding fungal infections of nail beds) - Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation - Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening - Active TB requiring treatment within the previous 3 years (participants previously treated for TB with no recurrence within 3 years are permitted). All Track tocilizumab-naïve participants must be screened for latent TB and if positive, should be treated following local practice guidelines prior to initiating tocilizumab - History of or currently active, primary or secondary immunodeficiency - Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including haematological malignancies and solid tumours, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that was excised and cured), or breast cancer diagnosed within the previous 20 years - History of alcohol, drug or chemical abuse within 1 year prior to screening - Pre-existing central nervous system (CNS) demyelination or seizure disorders - Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial | |
| 3 | NCT02579603 | completed | 1 | phase 4 | ['idiopathic pulmonary fibrosis'] | ["['J84.112']"] | ['nintedanib', 'pirfenidone'] | ['CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O', 'CC1=CN(C(=O)C=C1)C2=CC=CC=C2'] | Inclusion criteria: - Written informed consent consistent with ICH-GCP(The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use- Good clinical practice) and local laws, signed prior to any study procedures being performed (including any required washout) - Male or female patients aged greater than or equal to 40 years at visit 1 - Idiopathic Pulmonary Fibrosis (IPF) diagnosis, based upon the ATS (American Thoracic Society)/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT (Latin American Thoracic Association) 2011 guideline and confirmed by the investigator based on chest high resolution computed tomography (HRCT) scan performed within 12 months of visit 1 - FVC (Forced vital capacity) greater than or equal to 50% of predicted normal at visit 1 Exclusion criteria: - ALT (Alanine transaminase), AST (Aspartate aminotransferase)> 1.5 fold upper limit of normal (ULN) at visit 1 - Total bilirubin > 1.5 fold ULN at visit 1 - Relevant airways obstruction (i.e. pre-bronchodilator FEV1 (Forced Expiratory Volume in one second)/FVC <0.7) at visit 1 - History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1 - Bleeding Risk: Known genetic predisposition to bleeding, Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, dabigatran, heparin, hirudin etc) or high dose antiplatelet therapy, History of haemorrhagic central nervous system event within 12 months prior to visit 1, History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1, International normalised ratio (INR) > 2 at visit 1, Prothrombin time and partial thromboplastin time (PTT) > 150% of institutional ULN at visit 1 - Planned major surgery during the trial participation, including lung transplantation,major abdominal or major intestinal surgery. - History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1 - Severe renal impairment (Creatinine clearance <30 mL/min calculated by Cockcroft-Gault formula at visit 1) or end-stage renal disease requiring dialysis - Treatment with NAC (n-acetylcysteine), prednisone >15 mg daily or >30 mg every 2 days OR equivalent dose of other oral corticosteroids and/or fluvoxamine within 2 weeks of visit 2 - Treatment with azathioprine, cyclophosphamide, cyclosporine as well as any other investigational drug within 8 weeks of visit 2 - Previous treatment with pirfenidone - Permanent discontinuation of nintedanib in the past due to Adverse Events considered drug-related - Known hypersensitivity to nintedanib, pirfenidone, peanut or soya or to any of the excipients - A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial - Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment - Women who are pregnant, nursing, or who plan to become pregnant while in the trial - Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly5 for 28 days prior to and 3 months after nintedanib administration - Patients not able to understand and follow study procedures including completion of self administered questionnaires without help - Patients who require dose reduction and/or temporary interruption during the run-in period with nintedanib 150 mg bid - Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment) | |
| 4 | NCT02577016 | completed | 1 | phase 3 | ['type 2 diabetes mellitus'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['sitagliptin', 'placebo', 'ipragliflozin'] | ['C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)CC(CC3=CC(=C(C=C3F)F)F)N', 'C1=CC=C2C(=C1)C=C(S2)CC3=C(C=CC(=C3)C4C(C(C(C(O4)CO)O)O)O)F'] | Inclusion Criteria: - Type 2 diabetes mellitus - Inadequate glycemic control on diet/exercise therapy and ipragliflozin monotherapy - HbA1c ≥7.0% and ≤10.0% before study start Exclusion Criteria: - History of type 1 diabetes mellitus or a history of ketoacidosis - History of any of the following medications: thiazolidinediones (TZD) and/or insulin within 12 weeks prior to study participation, sitagliptin within 8 weeks prior to study participation. - Currently has a urinary tract infection or genital infection with subjective symptom | |
| 5 | NCT02571777 | completed | 1 | phase 3 | ['asthma'] | ["['J45.998', 'J82.83', 'J45.909', 'J45.991', 'J45.20', 'J45.30', 'J45.40']"] | ['qvm149 150/50/160', 'qvm149 150/50/80', 'qmf149 150/320', 'qmf149 150/160', 'salmeterol/fluticasone'] | ['Status: 400'] | Inclusion Criteria: - Patients with a diagnosis of asthma, (GINA 2015) for a period of at least 1 year prior to Visit 1 (Screening). - Patients who have used medium or high dose of ICS/LABA combinations for asthma for at least 3 months and at stable medium or high doses of ICS/LABA for at least 1 month prior to Visit 1. - Patients must be symptomatic at screening despite treatment with mid or high stable doses of ICS/LABA. Patients with ACQ-7 score ≥ 1.5 at Visit 101 and at Visit 102 (before randomization). - Patients with documented history of at least one asthma exacerbation which required medical care from a physician, ER visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1, and required systemic corticosteroid treatment. - Pre-bronchodilator FEV1 of < 80 % of the predicted normal value for the patient according to ATS/ERS guidelines after withholding bronchodilators at both visits 101 and 102. - Withholding period of bronchodilators prior to spirometry: SABA for ≥ 6 hrs, Twice daily LABA (or FDC of ICS/LABA) for ≥ 12 hrs, Once daily LABA (or FDC of ICS/LABA) for ≥ 24 hrs, SAMA for ≥ 8 hrs, Short acting xanthines for 12 hrs, Long acting xanthines for 24 hrs, . - Washout period of each drug should be kept as close as possible as above and should not be longer. If longer washout period is needed due to scheduling issues, please contact Novartis Medical monitor. - A one-time repeat of percentage predicated FEV1 (Pre-bronchodilator) at Visit 101 and/or Visit 102 is allowed in an ad-hoc visit. Repeat of Visit 101 spirometry should be done in an ad-hoc visit to be scheduled on a date that would provide sufficient time to receive confirmation from the spirometry data central reviewer of the validity of the assessment before randomization. Run-in medication should be dispensed once spirometry assessment met inclusion criteria (ATS/ERS quality criteria, FEV1 % predicted normal value, and reversibility) as per equipment - A one-time rescreen is allowed in case the patient fails to meet the criteria at the repeat, provided the patient returned to the required treatment as per inclusion criteria 4 - Patients who demonstrate an increase in FEV1 of 12% and 200 mL within 30 minutes after administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose) at Visit 101.All patients must perform a reversibility test at Visit 101. If reversibility is not demonstrated at Visit 101 then one of the following criteria need to be met. - Reversibility should be repeated once. - Patients may be permitted to enter the study with historical evidence of reversibility that was performed according to ATS/ERS guidelines within 2 years prior to Visit 1. - Alternatively, patients may be permitted to enter the study with a historical positive bronchoprovocation test that was performed within 2 years prior to Visit 1. If reversibility is not demonstrated at Visit 101 (or after repeated assessment in an ad-hoc visit) and historical evidence of reversibility/bronchoprovocation is not available (or was not performed according to the ATS/ERS guidelines patients must be screen failed - Spacer devices are permitted during reversibility testing only. The Investigator or delegate may decide whether or not to use a spacer for the reversibility testing Exclusion Criteria: - Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening). If patients experience an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit between Visit 1 and Visit 102 they may be re-screened 6 weeks after recovery from the exacerbation. - Patients who have ever required intubation for a severe asthma attack/exacerbation. - Patients who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study. - Patients treated with a LAMA for asthma within 3 months prior Visit 1 (Screening). - Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered). - Patients who have had a respiratory tract infection or asthma worsening as determined by investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and Visit 102. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening. - Patients with evidence upon visual inspection (laboratory culture is not required) of clinically significant (in the opinion of investigator) oropharyngeal candidiasis at Visit 102 or earlier, with or without treatment. Patients may be re-screened once their candidiasis has been treated and has resolved. - Patients with any chronic conditions affecting the upper respiratory tract (e.g. chronic sinusitis) which in the opinion of the investigator may interfere with the study evaluation or optimal participation in the study. - Patients with a history of chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis. - Patients with Type I diabetes or uncontrolled Type II diabetes. - Patients who, either in the judgment of the investigator or the responsible Novartis personnel, have a clinically significant condition such as (but not limited to) unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure arrhythmia, uncontrolled hypertension, cerebrovascular disease, psychiatric disease, neurodegenerative diseases, or other neurological disease, uncontrolled hypo- and hyperthyroidism and other autoimmune diseases, hypokalemia, hyperadrenergic state, or ophthalmologic disorder or patients with a medical condition that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. - Patients with paroxysmal (e.g., intermittent) atrial fibrillation are excluded. Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blockers, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at the run-in visit (Visit 101) with a resting ventricular rate < 100/min. At Visit 101 the atrial fibrillation must be confirmed by central reading. - Patients with a history of myocardial infarction (this should be confirmed clinically by the investigator) within the previous 12 months. - Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study - Patients with a history of long QT syndrome or whose QTc measured at Visit 101 (Fridericia method) is prolonged (> 450 msec for males and > 460 msec for females) and confirmed by a central assessor (these patients should not be rescreened). - Patients with a history of hypersensitivity to lactose, any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof. - Patients who have not achieved an acceptable spirometry result at Visit 101 in accordance with ATS/ERS criteria for acceptability and repeatability. A one-time repeat spirometry is allowed in an ad-hoc visit scheduled as close as possible from the first attempt (but not on the same day) if the spirometry did not qualify due to ATS/ERS criteria at Visit 101 and/or Visit 102. If the patient fails the repeat assessment, the patient may be rescreened once, provided the patient returns to the required treatment as per inclusion criteria 4. - Patients unable to use the Concept1 dry powder inhaler, Accuhaler or a metered dose inhaler. Spacer devices are not permitted. - History of alcohol or other substance abuse. - Patients with a known history of non-compliance to medication or who were unable or unwilling to complete a patient diary or who are unable or unwilling to use Electronic Peak Flow with e-diary device. - Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers). | |
| 6 | NCT02579382 | completed | 0 | phase 2 | ['chronic hepatitis b'] | ["['B18.0', 'B18.1', 'B18.2', 'B18.8', 'B18.9']"] | ['tdf', 'vesatolimod', 'placebo'] | ['CC(C)OC(=O)OCOP(=O)(COC(C)CN1C=NC2=C(N=CN=C21)N)OCOC(=O)OC(C)C.C(=CC(=O)O)C(=O)O', 'CCCCOC1=NC(=C2C(=N1)N(CC(=O)N2)CC3=CC=CC(=C3)CN4CCCC4)N'] | Key Inclusion Criteria: - Adult males or females between the ages of 18-65 - Chronic hepatitis B virus (HBV) infection - HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening Key Exclusion Criteria: - Extensive bridging fibrosis or cirrhosis - Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening - Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV) - Chronic liver disease other than HBV - Lactating or pregnant females or those that wish to become pregnant during the course of the study Note: Other protocol defined Inclusion/Exclusion criteria may apply. | |
| 7 | NCT02578121 | withdrawn | investigator decided to close study without enrollment | 0 | phase 2 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['ixazomib', 'pomalidomide', 'dexamethasone'] | ['B(C(CC(C)C)NC(=O)CNC(=O)C1=C(C=CC(=C1)Cl)Cl)(O)O', 'C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N', 'CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C'] | Inclusion Criteria: - Each patient must meet all of the following inclusion criteria to be enrolled in the study: - Male or female patients 18 years or older. - Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. - Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) - Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) - Patients must have a diagnosis of relapsed and/or refractory multiple myeloma and must have received at least one line of prior therapy. Patients must be at least 14 days beyond the last multiple myeloma therapy and have recovered from acute toxicities of prior therapies measured by CTCAE (Version 4.0) - Patients must have life expectancy of at least 3 months. - Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. - Patients must meet the following clinical laboratory criteria: Absolute neutrophil count (ANC) > 1,000/mm3 and platelet count> 50,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Total bilirubin <1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN. Calculated creatinine clearance > 30 mL/min (see APPENDIX C for the Cockcroft-Gault Equation)., Exclusion Criteria: - Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - Female patients who are lactating or have a positive serum pregnancy test during the screening period. - Failure to have fully recovered (ie, < Grade 1 toxicity) from the reversible effects of prior chemotherapy. - Major surgery within 14 days before enrollment. - Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval. - Central nervous system involvement. - Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. - Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. - Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. - Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. - Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. - Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of oral medications including difficulty swallowing. - Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. - Patient has > Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period. - Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial. |
| 8 | NCT02573935 | terminated | suspected side effects to the combination of clarithromycin and vcd (bortezomib, cyclophosphamide and dexamethasone) | 0 | phase 2 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['clarithromycin', 'placebo', 'vcd induction therapy'] | ['CCC1C(C(C(C(=O)C(CC(C(C(C(C(C(=O)O1)C)OC2CC(C(C(O2)C)O)(C)OC)C)OC3C(C(CC(O3)C)N(C)C)O)(C)OC)C)C)O)(C)O'] | Inclusion Criteria: - Myeloma diagnosis according to IMWG criteria - Treatment demanding disease - High-dose melphalan with stem cell support scheduled as a part of the treatment - Signed informed consent given prior to any study related activities - Age > 18 years Exclusion Criteria: - Allogeneic transplantation scheduled as a part of the treatment - Myeloma treatment prior to entry in the study, except radiotherapy, bisphosphonates/denosumab or corticosteroids for symptom control - Concurrent disease making clarithromycin treatment unsuitable - Positive pregnancy test (only applicable for women with childbearing potential) - Known or suspected hypersensitivity or intolerance to clarithromycin - Prolonged QT corrected (QTc) interval ( > 500 msec on screening ECG) - Concurrent treatment with cabergoline, fluconazole, ketoconazole, pimozide, quetiapine, sirolimus, verapamil, tacrolimus, ergot alkaloid, simvastatin or other statins - Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, uncontrolled angina or known cardiac amyloidosis - Severe renal dysfunction (estimated creatinine clearance <10 mL/min) - Serious medical or psychiatric illness which, in the judgment of the investigator, would make the patient inappropriate for entry into the study |
| 9 | NCT02577003 | completed | 1 | phase 3 | ['type 2 diabetes mellitus'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['ipragliflozin', 'placebo', 'sitagliptin'] | ['C1=CC=C2C(=C1)C=C(S2)CC3=C(C=CC(=C3)C4C(C(C(C(O4)CO)O)O)O)F', 'C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)CC(CC3=CC(=C(C=C3F)F)F)N'] | Inclusion Criteria: - Type 2 diabetes mellitus - Inadequate glycemic control on diet/exercise therapy and sitagliptin monotherapy - HbA1c ≥7.0% and ≤10.0% before study start Exclusion Criteria: - History of Type 1 diabetes mellitus or a history of ketoacidosis - History of any of the following medications: thiazolidinediones (TZD) and/or insulin within 12 weeks prior to study participation and sodium glucose cotransporter 2 (SGLT2) inhibitors anytime - Currently has a urinary tract infection or genital infection with subjective symptom | |
| 10 | NCT02579681 | completed | 1 | phase 3 | ['multiple sclerosis, relapsing-remitting'] | ["['G35', 'G93.81', 'K74.1', 'Q85.1', 'G12.21', 'G12.23', 'M34.0']"] | ['dimethyl fumarate'] | ['COC(=O)C=CC(=O)OC'] | Key Inclusion Criteria: - Must have a confirmed diagnosis of RRMS according to McDonald criteria (Polman, Reingold et al. 2005). - Must have a baseline EDSS between 0.0 and 5.0, inclusive. - Must have experienced at least 1 relapse within the 12 months prior to randomization, with a prior brain MRI demonstrating lesion(s) consistent with MS, or show evidence of gadolinium-enhancing lesion(s) of the brain on an MRI performed within the 6 weeks prior to randomization. Key Exclusion Criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of screening: - Primary progressive, secondary progressive, or progressive relapsing MS, as defined by Lublin and Reingold (Lublin and Reingold 1996) - Severe depression (MADRS score >34) (Montgomery and Asberg 1979) - History of malignancy (except basal cell carcinoma that has been completely excised prior to study enrollment) - An MS relapse that has occurred within the 30 days prior to inclusion AND/OR the participant has not stabilized from a previous relapse prior to inclusion. | |
| 11 | NCT02573870 | completed | 0 | phase 2 | ['pulmonary disease, chronic obstructive'] | ["['J44.9', 'J44.1', 'J44.0']"] | ['batefenterol + fluticasone furoate', 'placebo', 'albuterol'] | ['CC(C)(C)NCC(C1=CC(=C(C=C1)O)CO)O'] | Inclusion Criteria: - Type of subject: Outpatient. - Informed Consent: Capable of giving signed informed consent, which includes compliance with pre-specified requirements and restrictions. - Age and gender: Male and female subjects, 40 years of age or older at the time of signing the informed consent, are eligible to participate in the study. Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential defined as: Pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. 2. Reproductive potential and agrees to follow one of the options listed below 30 days prior to the first dose of study medication and until at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer after the last dose of study medication and completion of the follow-up visit. This list does not apply to females of reproductive potential with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label Oral Contraceptive, either combined or progestogen alone Injectable progestogen Contraceptive vaginal ring Percutaneous contraceptive patches Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. - Chronic Obstructive Pulmonary Disease (COPD): An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society. - COPD Disease severity: A post-albuterol forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of =<0.70 and a post-albuterol FEV1 >=30 and =<80% of predicted normal values calculated using the European Respiratory Society Global Lung Function Initiative reference equations at Visit 1. - Smoking history: Current or former cigarette smokers with a history of cigarette smoking of >= 10 pack-years at Visit 1. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Number of pack years = (number of cigarettes per day / 20) x number of years smoked (for example, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years). Note: Pipe and cigar use cannot be used to calculate pack-year history. Exclusion Criteria: - Asthma: A current diagnosis of asthma (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD). - Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. Other excluded conditions include and not limited to clinically significant bronchiectasis, pulmonary hypertension unrelated to COPD, sarcoidosis, or interstitial lung disease. Or a subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD - Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. - Poorly controlled COPD: defined as the occurrence of 'acute worsening of COPD that is managed with corticosteroid and/or antibiotics or that requires treatment prescribed by a physician in the 6 weeks prior to Screening (Visit 1)', or 'subjects who are hospitalized due to acute worsening of COPD within 12 weeks of Visit 1'. - History of COPD exacerbation: subject who have had more than one exacerbation (moderate or severe) within the 12 months prior to Visit 1. - Pneumonia and lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1; or subjects hospitalized due to pneumonia within 12 weeks of Visit 1. - Use of long-term oxygen therapy (LTOT): Oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (that is, =<12 hours per day) is not exclusionary. - Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (for example, albuterol) via nebulized therapy. - Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1. - Clinically significant abnormal laboratory finding at Visit 1. - Liver Disease: Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). - Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid polymerase chain reaction test is obtained. - Abnormal and clinically significant findings from 12-lead electrocardiogram (ECG) performed at Visit 1. Site investigators will be provided with ECG over-read conducted by a centralized independent cardiologist, to assist in evaluation of subject eligibility. For this study, an abnormal and clinically significant ECG that would preclude a subject from entering the trial is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following: Sinus bradycardia <45 beats per minute (bpm) (Note: Sinus bradycardia <45 bpm should be confirmed by two additional readings at least 5 minutes apart) Sinus tachycardia >=110 bpm (Note: Sinus tachycardia >=110 should be confirmed by two additional readings at least 5 minutes apart) Multifocal atrial tachycardia (wandering atrial pacemaker with rate >100 bpm) PR interval >240 milliseconds (msec) Evidence of Mobitz II second degree or third degree atrioventricular (AV) block Pathological Q waves (defined as wide [>0.04 seconds] and deep [>0.4 millivolt (mV) (4 millimeters [mm] with 10 mm/mV setting)] or >25% of the height of the corresponding R wave, providing the R wave was >0.5 mV [5 mm with 10 mm/mV setting], appearing in at least two contiguous leads (Note: prior evidence [that is, ECG obtained at least 12 months prior) of pathological Q waves that are unchanged are not exclusionary; and the investigator will determine if the subject is precluded from entering the study) Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal premature ventricular complexes. For subjects without complete right bundle branch block: QT interval corrected by Fridericia's method (QTc[F]) >=450 msec or an ECG that is unsuitable for QT measurements (for example, poor defined termination of the T wave) For subjects with complete right bundle branch block: QTc(F) >=480msec or an ECG that is unsuitable for QT measurements (for example, poor defined termination of the T wave) (Note: All potentially exclusionary QT measurements should be confirmed by two additional readings at least 5 minutes apart) ST-T wave abnormalities (excluding non-specific ST-T wave abnormalities) (Note: prior evidence (that is, ECG obtained at least 12 months prior) of ST-T waves that are unchanged are not exclusionary and the investigator will determine if the subject is precluded from entering the study) Clinically significant conduction abnormalities (for example, Wolff-Parkinson-White syndrome or bifascicular block defined as complete left bundle branch block or complete right bundle branch block with concomitant left fascicular block) Clinically significant arrhythmias (for example, atrial fibrillation with rapid ventricular response, ventricular tachycardia) - Medication Prior to Spirometry: Unable to withhold albuterol for the 4 hour period required prior to spirometry testing at each study visit. - Excluded Medications: Use of the following medications are not permitted within the defined time intervals prior to Visit 1 and throughout the study: Depot corticosteroids: 12 weeks Systemic, oral or parenteral corticosteroids: 6 weeks Antibiotics (for lower respiratory tract infection): 6 weeks 'Cytochrome P450 3A4' strong inhibitors and 'P-glycoprotein' inhibitor: 4 weeks Long acting beta-agonist (LABA)/inhaled corticosteroid (ICS) combination products : 4 weeks ICS : 4 weeks Phosphodiesterase 4 (PDE4) inhibitors (roflumilast): 1 week LABA/ Long-acting muscarinic antagonist (LAMA) combination (for example, vilanterol/umeclidinium bromide): 1 week Once-daily beta2-agonist (for example, Olodaterol and Indacaterol): 1 week LAMA (tiotropium, aclidinium, glycopyrronium, umeclidinium): 1 week Theophylline preparations: 48 hours Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton): 48 hours Oral beta2-agonists Long-acting: 48 hours Short-acting: 12 hours Inhaled LABA (for example, Salmeterol, formoterol): 48 hours Inhaled sodium cromoglycate or nedocromil sodium: 24 hours Inhaled short acting beta2-agonists: 4 hours Inhaled short-acting anticholinergics: 4 hours Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products: 4 hours Use of study provided albuterol is permitted during the study, except in the 4-hour period prior to spirometry testing - Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1. - Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta-2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) lactose/milk protein, or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction, that, in the opinion of the study physician contraindicates study participation or use of an inhaled LAMA, LABA or ICS - The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) - Affiliation with Investigator Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator. - Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a diary. - Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study. - Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits. | |
| 12 | NCT02575300 | completed | 0 | phase 2 | ['carcinoid tumors', 'pancreatic net'] | ["['C7A.00', 'C7A.010', 'C7A.011', 'C7A.012', 'C7A.020', 'C7A.021', 'C7A.026']"] | ['ibrutinib'] | ['C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N'] | Inclusion Criteria: - Locally unresectable or metastatic carcinoid or pancreatic neuroendocrine tumors (pNETs) - Measureable disease by Response Evaluation Criteria in Solid Tumors (RECIST) - Tumors must be histologically or cytologically proven and considered low or intermediate grade. Patients with high grade neuroendocrine carcinomas or small cell carcinomas are excluded from the study. - Evidence of progressive disease within 12 months of study entry - Allowed prior therapies include: a) Surgery (major surgery at least more than four weeks prior to baseline assessment); b) Locoregional therapy such as: chemoembolization, radio-embolization, radiofrequency ablation, radiotherapy as long as there is progressive measurable disease outside the area of locoregional therapy or there is progression in the previously treated areas; c) Any number of previous lines of systemic therapy. Last treatment before enrollment must have occurred more than 4 weeks for chemotherapy, 6 weeks for antibodies or more than 5 half-lives of prior tyrosine kinase inhibitors (TKIs) or small molecules. - Prior or concurrent therapy with somatostatin analogs is permitted for patients with secretory NET - All patients with gastroenteropancreatic NETs must have progressed on (or are intolerant of) prior somatostatin analog. - Patients with pancreatic NETs must have progressed on (or are intolerant of) either everolimus or sunitinib. - Age ≥ 18 years - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 - Life expectancy 12 weeks or more - Adequate bone marrow function as shown by: absolute neutrophil count ≥ 1,000/mm^3, Platelets ≥ 100,000/mm^3, Hb > 10 g/dl - Adequate liver function as shown by: serum bilirubin ≤ 1.5 x ULN, and serum transaminases activity ≤ 2.5 x ULN, with the exception of serum transaminases (< 3 x ULN) if the patient has liver metastases - Adequate renal function as shown by serum creatinine ≤ 2 mg/dl - Women of childbearing potential must have a negative serum pregnancy test within 7 days of the administration of the first study treatment. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study. - Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information. Exclusion Criteria: - High grade NET or small cell neuroendocrine carcinoma - Clinically apparent central nervous system metastases or carcinomatous meningitis - Known positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) - History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug - Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class III or IV cardiac disease as defined by the New York Heart Association (NYHA) functional classification - Requirement for anticoagulation with warfarin or similar vitamin K antagonists. - Requirement for treatment with a strong cytochrome P450 (CYP) 3A4/5 - Prior antitumor therapy within 2 weeks of enrollment (with the exception of somatostatin analogs) - No other active malignancy within 3 years of enrolment except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years - Any medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib - Known hypersensitivity to ibrutinib or any component of the ibrutinib formulation - History of noncompliance to medical regimens or unwillingness to comply with the protocol - Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification | |
| 13 | NCT02578680 | completed | 1 | phase 3 | ['non-small-cell lung carcinoma'] | ["['D02.20', 'D02.21', 'D02.22']"] | ['cisplatin', 'carboplatin', 'pemetrexed', 'dexamethasone 4 mg', 'saline solution'] | ['N.N.Cl[Pt]Cl', 'C1CC(C1)(C(=O)O)C(=O)O.[NH2-].[NH2-].[Pt+2]', 'C1=CC(=CC=C1CCC2=CNC3=C2C(=O)NC(=N3)N)C(=O)NC(CCC(=O)O)C(=O)O'] | Inclusion Criteria: - Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC. - Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated. - Has measurable disease. - Has not received prior systemic treatment for their advanced/metastatic NSCLC. - Can provide tumor tissue. - Has a life expectancy of at least 3 months. - Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status. - Has adequate organ function - If female of childbearing potential, is willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. - If male with a female partner(s) of child-bearing potential, must agree to use adequate contraception starting with the first dose of study medication through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. Exclusion Criteria: - Has predominantly squamous cell histology NSCLC. - Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab. - Before the first dose of study medication: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy (e.g., erlotinib, crizotinib, cetuximab), c) Had major surgery (<3 weeks prior to first dose) - Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study medication. - Completed palliative radiotherapy within 7 days of the first dose of study medication. - Is expected to require any other form of antineoplastic therapy while on study. - Received a live-virus vaccination within 30 days of planned start of study medication. - Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis. - Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb). - Known sensitivity to any component of cisplatin, carboplatin or pemetrexed. - Has active autoimmune disease that has required systemic treatment in past 2 years. - Is on chronic systemic steroids. - Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). - Is unable or unwilling to take folic acid or vitamin B12 supplementation. - Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab study and has been treated with pembrolizumab. - Has an active infection requiring therapy. - Has known history of Human Immunodeficiency Virus (HIV). - Has known active Hepatitis B or C. - Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. - Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol). - Has symptomatic ascites or pleural effusion. - Has interstitial lung disease or a history of pneumonitis that required oral of IV glucocorticoids to assist with management. - Is pregnant or breastfeeding, or expecting to conceive or father children prior to 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. | |
| 14 | NCT02578537 | unknown status | 1 | phase 4 | ['non st segment elevation acute coronary syndrome', 'chronic kidney disease'] | ["['I12.9', 'N18.9', 'I12.0', 'D63.1', 'N18.1', 'N18.5', 'I13.0']"] | ['ticagrelor', 'clopidogrel'] | ['CCCSC1=NC(=C2C(=N1)N(N=N2)C3CC(C(C3O)O)OCCO)NC4CC4C5=CC(=C(C=C5)F)F', 'COC(=O)C(C1=CC=CC=C1Cl)N2CCC3=C(C2)C=CS3'] | Inclusion Criteria: - P2Y12 inhibitor naïve patients presenting with NSTE-ACS (unstable angina or non-ST segment elevation myocardial infarction). - Males and non-pregnant females > 18 years of age. - eGFR<60 ml/min/1.73m2 (MRDR formula). - With planned percutaneous coronary intervention(PCI will be performed over 24 hours after loading dose). - Written informed consent provided.Provision of informed consent prior to any study specific procedures. Exclusion Criteria: - Cardiogenic shock. - Thrombolytic therapy administered before randomization. - Active bleeding or bleeding predisposition, including the retinal or vitreous hemorrhage , gastrointestinal or urinary tract hemorrhage , history of intracranial haemorrhage or cerebral infarction . - Hypersensitivity to ticagrelor or any excipients. - Deep puncture or major surgery within 1 month. - Untreated or uncontrolled hypertension with blood pressure >180/110 mmHg. - Known hemoglobin <10 g/dL or platelet count <100 × 109/L. - Known moderate or severe hepatic impairment. - Known aminotransferase level >3x the upper limit of normal. - Known allergy to any of the study drugs or devices (aspirin, clopidogrel, ticagrelor stainless steel, contrast agents, etc.). - Pregnancy or lactation. - Any condition which might interfere with study compliance, or otherwise unsuitable for study participation as judged by the investigators. - Unwilling or unable to get repeat platelet assay or clinical follow-up. - Unwilling or unable to provide written informed consent. | |
| 15 | NCT02570490 | completed | 1 | phase 3 | ['acute bacterial skin and skin structure infections'] | ["['A49.9', 'G00.8', 'G00.9', 'J15.9', 'K65.2', 'A04.9', 'A05.9']"] | ['sodium fusidate', 'linezolid'] | ['CC1C2CCC3(C(C2(CCC1O)C)C(CC4C3(CC(C4=C(CCC=C(C)C)C(=O)[O-])OC(=O)C)C)O)C.[Na+]', 'CC(=O)NCC1CN(C(=O)O1)C2=CC(=C(C=C2)N3CCOCC3)F'] | Inclusion Criteria: - Adolescents between 12 to 18 years old must weigh >60 kg - Patients diagnosed with ABSSSI with at least one systemic sign of infection - Diagnosed with cellulitis, major cutaneous abscess, or wound infections (traumatic or surgical) - Surface redness, edema or induration must be of a minimum surface area of 75 cm2, or extending ≥5 cm from the peripheral margin of the abscess - Suspected or documented ABSSSI caused by a Gram-positive pathogen Exclusion Criteria: - Involving a chronic diabetic foot infection (diabetic foot ulcer) - Involving burns - Involving an anatomical location (e.g. perirectal area) where the incidence of Gram-negative and/or anaerobic pathogen involvement is likely - Documented bacteremia associated with the current ABSSSI - Known severe renal impairment, as indicated by estimated CrCl <30 mL/min (by Cockcroft-Gault calculation) - Evidence of significant liver disease: ALT >3x ULN, or direct bilirubin >ULN; known cirrhosis with decompensation (i.e. Child-Pugh Class B or C disease) | |
| 16 | NCT02649686 | completed | 0 | phase 1 | ['metastatic breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['durvalumab', 'trastuzumab'] | ['Status: 503'] | Inclusion Criteria: - Patients must have histologically and/or cytologically confirmed HER-2 positive (assessed locally and by current ASCO/CAP criteria) breast cancer that is advanced/metastatic/recurrent or unresectable and for which no curative therapy exists. - Patients enrolled to the RP2D / expansion cohort must have accessible disease suitable for biopsy and have consented to biopsy prior to treatment and at the end of cycle 1. Paired biopsies are strongly recommended in all patients. - Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative). - All patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows: - Chest x-ray ≥ 20 mm - CT scan (with slice thickness of 5 mm) ≥ 10 mm to longest diameter - Physical exam (using calipers) ≥ 10 mm - Lymph nodes by CT scan ≥ 15 mm to measured in short axis - Patients must be ≥ 18 years of age. - Patients must have an ECOG performance status of 0, 1, or 2. Previous Therapy - Must have had prior exposure to a taxane, trastuzumab and pertuzumab* and preferably also prior exposure to TDM-1. - Taxane and pertuzumab may have been in the adjuvant or neoadjuvant setting. - Must not be eligible for further trastuzumab treatment per provincial / formulary guidelines (i.e. patient has had two prior lines of either trastuzumab or lapatinib). - Must have received at least one HER-2 based therapy in the palliative setting. * Note: exceptions to the requirement for prior pertuzumab may be given. Consult CCTG. Cytotoxic Chemotherapy: - There is no limit to the number of prior regimens. Other Systemic Therapy: - There is no limit to the number of prior regimens; however, patients may not have had prior immune therapies. - Patients must have recovered from all reversible toxicity related to prior chemotherapy or systemic therapy and have adequate washout as follows: - Longest of one of the following: - Two weeks, - 5 half-lives for investigational agents, - Standard cycle length of standard therapies. - Radiation: - Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of registration. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with NCIC CTG. Concurrent radiotherapy is not permitted. - Surgery: - Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred. - Laboratory Requirements (must be done within 7 days prior to registration) - Hematology - Absolute neutrophils ≥ 1.0 x 109/L - Platelets ≥ 100 x 109/L - Hemoglobin ≥ 90 g/L - Chemistry - Bilirubin ≤ 1.5 x ULN (upper limit of normal)* - AST and ALT ≤ 2.5 x ULN & ≤ 5.0 x ULN if patient has liver metastases - Serum creatinine < 1.25 x ULN or: Creatinine clearance** ≥ 40 mL/min - Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception while on study and for 90 days after the last dose of durvalumab and consult product monograph for trastuzumab. Male partners of a female subject and non-sterilized male patients who are sexually active with a female partner of childbearing potential must use male condom plus spermicide while on study and for 90 days after the last dose of durvalumab and consult product monograph for trastuzumab. Female partners of a male subject must use a highly effective method of contraception throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. - Subjects should not donate blood while participating in this study, or for at least 90 days following the last infusion of durvalumab, or until the time specified in the prescribing information of trastuzumab, whichever occurs longest. - Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to registration in the trial and prior to tests which are considered to be study specific to document their willingness to participate. - Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients) are not to be recruited into the study. Patients competent but physically unable to sign the consent form may have the document signed by their nearest relative or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested. - Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. - In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient registration. Exclusion Criteria: - Patients with a history of other malignancies requiring concurrent anticancer therapy. - Patients with brain metastases are eligible providing that they have been treated, are stable (CT scan prior to enrolment mandatory for patients with known brain metastases) and patients are on a stable or decreasing dose of steroids (no more than equivalent of prednisone 10mg). - Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 2 years prior to the start of treatment. The following are exceptions to this criterion: patients with vitiligo or alopecia, Graves' disease, hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment (within the past 2 years). - History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of registration or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy (NOTE: Intranasal/inhaled corticosteroids or systemic steroids that do not to exceed 10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are permissible.) - Live attenuated vaccination administered within 30 days prior to registration or within 30 days of receiving durvalumab. - Any previous treatment with a PD-1 or PD-L1 inhibitor, or other immune based therapy including durvalumab. - History of hypersensitivity to durvalumab or trastuzumab or any excipient. - Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 ECGs using Fredericia's Correction. - Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients should have a LVEF ≥ 50%. - Concurrent treatment with other investigational drugs or anti-cancer therapy. - Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to: - History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study compliance. - Active infection (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis or any infection requiring systemic therapy). - active peptic ulcer disease or gastritis - Pregnant or lactating women. Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration. If test is positive, pregnancy testing may then include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy. | |
| 17 | NCT02641028 | completed | 0 | phase 2 | ['smoking'] | ["['O99.334', 'O99.335', 'Y93.G2', 'O99.330', 'O99.331', 'O99.332', 'O99.333']"] | ['cerc-501', 'placebo'] | ['CC1=CC(=CC(=C1)C2CCCN2CC3=CC=C(C=C3)OC4=C(C=C(C=C4)C(=O)N)F)C'] | Inclusion Criteria: 1. Provides written informed consent and agrees to complete required clinic visits 2. Male or female 21 to 60 years of age inclusive 3. Body mass index (BMI) 18.5 to 40 kg/m2 inclusive 4. Heavy Smokers 5. Currently not seeking smoking cessation therapy 6. In otherwise good general health without any unstable medical conditions (as determined by medical history, medication history, physical examination, 12-lead ECG, vital signs, and clinical laboratory testing) 7. Able to read, write, and speak in English 8. Females must be either: - Post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile -or- - Women of childbearing potential (WOCBP) must meet the criteria below: - Uses an acceptable double-barrier method of contraception as determined by the Investigator -and- - Is not lactating, has a negative serum beta human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test prior to dosing on Days 1 and 8 of each treatment period. 9. Male subjects must agree to use a condom if partner is of childbearing potential Exclusion Criteria: Subjects meeting the following criteria are not eligible for the study: 1. Any substance use disorder other than nicotine or caffeine as assessed by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) substance use disorder checklist in addition to the Mini-International Neuropsychiatric Interview (MINI) (to capture both DSM-V substance use disorder diagnoses) 2. Current neurological conditions that interfere with study conduct, assessment or treatment in any significant fashion 3. Any lifetime history of bipolar I, II; schizophrenia or any other psychotic disorders; personality disorders, impulse control disorders as assessed by the MINI 4. Current psychiatric conditions that interfere with study conduct, assessment or treatment in any significant fashion, such as major depressive disorder (MDD), eating disorders, post-traumatic stress disorder, etc., without permission of the medical monitor 5. Recent active or past history of gastric disease such as peptic ulcer disease, gastritis, upper gastrointestinal bleeding, or any gastrointestinal malignancy or precancerous condition 6. Active, comorbid disease that might limit the ability of the subject to participate in the study as determined by the Investigator (i.e., poorly controlled diabetes mellitus, congestive heart failure, etc.) 7. Clinically significant clinical laboratory test taken during screening, without permission of the Medical Monitor 8. Elevated AST or ALT ≥ 2 times the upper limit of normal (ULN) 9. Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C positive as determined by serology testing at Screening 10. History of severe allergies or multiple adverse drug reactions 11. Known hypersensitivity to CERC-501 12. Current use of a proton pump inhibitor or histamine 2 blocker without permission of the Medical Monitor 13. Use of any investigational medication within 2 months prior to the start of this study or scheduled to receive an investigational drug other than the study drug during the course of this study | |
| 18 | NCT02642432 | completed | 1 | phase 3 | ['hepatitis c virus infection', 'chronic hepatitis c', 'compensated cirrhosis'] | ["['B00.81', 'B25.1', 'B26.81', 'B58.1', 'K75.4', 'A51.45', 'B17.2']", "['B18.2', 'B18.0', 'B18.1', 'B18.8', 'B18.9', 'K71.3', 'K71.4']", "['K74.3', 'K74.4', 'K74.5', 'K74.60', 'K74.69', 'P78.81', 'K70.30']"] | ['abt-493/abt-530'] | ['Status: 400'] | Inclusion Criteria: - Screening laboratory result indicating hepatitis C virus (HCV) Genotype 1, 2, 4, 5 or 6 (GT1,2,4,5,6) infection - Chronic HCV infection - Subject must be HCV treatment-naïve or have failed prior HCV treatment - Subject must have documented compensated cirrhosis and no current or past clinical evidence of decompensated liver disease Exclusion Criteria: - Positive test result at screening for Hepatitis B surface antigen or anti-human immunodeficiency virus (anti-HIV) antibody - HCV genotype performed during screening indicating co-infection with more than 1 HCV genotype - Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-493/ABT-530 | |
| 19 | NCT02648204 | completed | 1 | phase 3 | ['diabetes', 'diabetes mellitus, type 2'] | ["['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']", "['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['semaglutide', 'dulaglutide'] | ['CCC(C)C(C(=O)NC(C)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)C(CC3=CC=CC=C3)NC(=O)C(CCC(=O)O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(=O)N)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC5=CC=CC=C5)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(C)(C)NC(=O)C(CC6=CN=CN6)N'] | Inclusion Criteria: - Male or female, age at least 18 years at the time of signing informed consent. - HbA1c (glycosylated haemoglobin) 7.0 - 10.5% (53 - 91 mmol/mol) (both inclusive) - Subjects on stable diabetes treatment with metformin (minimum of 1500 mg/day or maximal tolerated dose documented in the patient medical record) for 90 days prior to screening Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) - Any condition, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term insulin treatment for acute illness for a total of equal to or below 14 days - History of pancreatitis (acute or chronic) - Screening calcitonin equal to or above 50 ng/L - Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma - Renal impairment defined as eGFR (electronic case report form) below 60 mL/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Subjects presently classified as being in New York Heart Association Class IV - Planned coronary, carotid or peripheral artery revascularisation on the day of screening - Proliferative retinopathy or maculopathy requiring acute treatment - History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas) - Anticipated initiation or change in concomitant medications (for more than 14 consecutive days or on a frequent basis) known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids) | |
| 20 | NCT02643420 | completed | 1 | phase 3 | ['neutropenia', 'breast cancer'] | ["['D70.4', 'D70.8', 'D70.9', 'P61.5', 'D70.3']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['spi-2012', 'pegfilgrastim', 'docetaxel', 'cyclophosphamide'] | ['CC(C(C(=O)O)N)OC1C(C(C(C(O1)COC2(CC(C(C(O2)C(C(CO)O)O)NC(=O)CNC(=O)OCCOC)O)C(=O)O)O)O)NC(=O)C', 'CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)O)C)O', 'Status: 503'] | Key Inclusion Criteria: - New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer - Candidate for adjuvant or neoadjuvant TC chemotherapy - Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 - Absolute neutrophil count (ANC) ≥ 1.5×10^9/L - Platelet count ≥ 100×10^9/L - Hemoglobin > 9 g/dL - Creatinine clearance > 50 mL/min - Total bilirubin ≤ 1.5 mg/dL - Aspartate Aminotransferase per Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase per Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5× Upper Limit of Normal (ULN). - Alkaline phosphatase ≤ 2.0×ULN Key Exclusion Criteria: - Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease - Locally recurrent or metastatic breast cancer - Known sensitivity to E. coli -derived products or to any products to be administered during dosing - Concurrent adjuvant cancer therapy - Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug - Active infection, receiving anti-infectives, or any serious underlying medical condition that would impair ability to receive protocol treatment - Prior bone marrow or stem cell transplant - Use of any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study - Radiation therapy within 30 days prior to enrollment - Major surgery within 30 days prior to enrollment | |
| 21 | NCT02640157 | completed | 1 | phase 3 | ['chronic hepatitis c', 'hepatitis c virus', 'genotype 3 hepatitis c virus'] | ["['B18.2', 'B18.0', 'B18.1', 'B18.8', 'B18.9', 'K71.3', 'K71.4']", "['B00.81', 'B25.1', 'B26.81', 'B58.1', 'K75.4', 'A51.45', 'B17.2']"] | ['abt-493/abt-530', 'sofosbuvir', 'daclatasvir'] | ['Status: 400', 'CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3', 'CC(C)C(C(=O)N1CCCC1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)C6CCCN6C(=O)C(C(C)C)NC(=O)OC)NC(=O)OC'] | Inclusion Criteria: - Male or female (of nonchildbearing potential, practicing total abstinence, sexually active with female partners only, or using allowed contraceptive methods) at least 18 years of age at time of screening. - Screening laboratory result indicating HCV GT3 infection. - Chronic HCV infection, defined as one of the following: - Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening; or - A liver biopsy consistent with chronic HCV infection; or - Abnormal alanine aminotransferase (ALT) levels for at least 6 months before screening. - Hepatitis C virus treatment-naïve (i.e., participant had never received any anti-HCV treatment). - Documented as noncirrhotic. Exclusion Criteria: - Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study. - Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could have precluded adherence to the protocol in the opinion of the investigator. - Positive test result at screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus Ab (HIV Ab). - Hepatitis C virus genotyping performed during screening indicated co-infection with more than one HCV genotype. - Any cause of liver disease other than chronic HCV infection. - Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493/ABT-530, SOF, or DCV. - History of severe, life-threatening, or other significant sensitivity to any excipients of the study drug. - Previous use of any anti-HCV treatment. | |
| 22 | NCT02644057 | withdrawn | could not enroll patients | 0 | phase 2 | ['cardiorenal syndrome'] | ["['Q93.81', 'B33.4', 'A36.81', 'A50.54', 'A52.00', 'A52.09', 'B33.24']"] | ['milrinone', 'dobutamine'] | ['CC1=C(C=C(C(=O)N1)C#N)C2=CC=NC=C2', 'CC(CCC1=CC=C(C=C1)O)NCCC2=CC(=C(C=C2)O)O'] | Inclusion Criteria: 1. Age >18 years 2. Admitted to the hospital with a primary diagnosis of Decompensated Heart Failure 3. Onset of cardio-renal syndrome (increasing creatinine>0.3mg/dl) after or before hospitalization. After hospitalization within 7 days of from the time of admission after receiving intravenous diuretics and heart failure medication optimization. Before hospitalization in the setting of escalating doses of outpatient loop diuretics and heart failure medication optimization 4. Persistent volume overload- For patients with a pulmonary artery catheter, peristent volume overload will include : Pulmonary capillary wedge pressure >22mm Hg and one of the following clinical signs :2+ peripheral edema and/or pulmonary edema or pleural effusion on chest Xray. For patients without a pulmonary artery catheter- persistent volume overload will include atleast 2 of the following: 2+ peripheral edema , jugular venous pressure >10 mm Hg and pulmonary edema or pleural effusion on chest Xray 5. BNP>400 6. Cr-1.2-3.0 Exclusion Criteria: 1. Intravascular volume depletion 2. Acute coronary syndrome within 4 weeks 3. Indication for hemodialysis 4. Systolic Blood pressure <90mm Hg or MAP<60mm Hg at the time of enrollment 5. Alternate explanation for worsening renal function , such as obstructive nephropathy , contrast induced nephropathy , ATN 6. Clinical instability likely to require the addition of intravenous vasoactive drugs including vasodilators and/or inotropic drugs 7. The use of iodinated radio-contrast material in the past 72 hours or anticipated use of intravenous contrast during the current hospitalization 8. Underlying rhythm disorder |
| 23 | NCT02640573 | terminated | insufficient accrual | 0 | phase 2 | ['hemoglobin sc disease'] | ["['D56.5', 'D56.4', 'D58.2', 'D59.5', 'D59.6', 'R82.3']"] | ['hydroxyurea'] | ['C(=O)(N)NO'] | Inclusion Criteria: - Diagnosis of HbSC disease - Score of 80 or lower on the AdultQLTM 3.0 Sickle Cell Disease Module, or any disease related complication, including, but not limited to, one or more pain events per year, proliferative sickle retinopathy, avascular necrosis, cholelithiasis, or any thrombotic event. If the subject has a score >80, they may still enroll on the trial, and be analyzed for secondary endpoints. They will be excluded from analysis of the primary endpoint. Exclusion Criteria: - Failure to meet inclusion criteria - Hydroxyurea usage in the last 3 months. - Chronic RBC transfusion therapy - Packed red blood cell transfusion in the last 3 months (temporary exclusion). - Pregnancy, or refusal to use medically effective birth control if female and sexually active. - Current phlebotomy therapy |
| 24 | NCT01824823 | terminated | slow accrual | 0 | phase 2 | ['head and neck squamous cell carcinoma'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['afatinib'] | ['CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4'] | Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Patients must have pathological evidence of persistent primary and/or lymph node disease with viable tumor cells following primary concurrent chemoradiotherapy of locoregionally advanced (stage III/IV) HNSCC of the oral cavity, oropharynx, larynx, hypopharynx or p16-positive unknown primary of the head and neck region; persistent primary and/or lymph node disease with viable tumor cells will be determined by the histological determination of tumor viability defined as tumor cells with intact cellular compartments (i.e. cytoplasm and nucleus) that do not exhibit karyolysis, pyknosis, or karyorrhexis on haematoxylin and eosin (H&E) staining - Patients must have undergone a neck dissection following completion of chemoradiotherapy and must have involved at the minimum a compartment dissection of nodal levels with residual abnormalities on post-treatment imaging studies and/or received a complete resection of the residual primary lesion with negative margins - Patients must have achieved a complete response at the primary disease site after chemoradiotherapy or complete resection of the residual primary site disease with negative margins - All persistent lymph node disease must have received at least 66 Gy of radiotherapy and must have been completely surgically resected prior to registration, and surgical incisions should be adequately healed - Patients with extracapsular lymph node extension, perineural or lymphovascular invasion will be eligible - Patients must be at least 6 weeks (42 days) and no more than 36 weeks (252 days) from completion of chemoradiation at the time of registration - Patients will be eligible regardless of ability to swallow; patients with dysphagia may have afatinib/placebo administered via gastrostomy tube - Absolute neutrophil count >= 1,000/mm^3 - Platelets >= 100,000/mm^3 - Total bilirubin =< 1.5 x the upper limit of normal (ULN) - Aspartate amino transferase (AST) =< 3 x the ULN - Alanine amino transferase (ALT) =< 3 x the ULN - Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula - Prior cetuximab or any epidermal growth factor receptor (EGFR) inhibitors will not be permitted including cetuximab administered with a chemoradiotherapy or radiotherapy regimen - As all patients in this study will have received prior full dose, curative-intent external-beam radiotherapy to the involved neck, no additional external-beam radiotherapy will be permitted prior to or during study participation - Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception - Patients must have electrocardiogram (ECG) within 8 weeks prior to randomization to the study - Patients must be assessed for cardiac function by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 8 weeks prior to randomization Exclusion Criteria: - Patients with known distant metastatic disease or with any gross residual disease following salvage primary tumor resection or neck dissection - Known hypersensitivity to afatinib or any of the excipients of this product - Prior adjuvant chemotherapy (aside from the initial induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy regimen) - History of acute myocardial infarction within 3 months prior to registration, and any history of uncontrolled angina, uncontrolled arrhythmia, or uncontrolled heart failure - Pregnant or breast-feeding women - Active infections, other cancers, or history of other cancers - Participation in any other clinical trials or taking any other experimental medications - Left ventricular dysfunction - Evidence of interstitial lung disease |
| 25 | NCT01825512 | completed | 1 | phase 3 | ['chronic iron overload'] | ["['E87.70', 'E87.79', 'E87.71']"] | ['deferiprone', 'deferasirox'] | ['CC1=C(C(=O)C=CN1C)O', 'C1=CC=C(C(=C1)C2=NN(C(=N2)C3=CC=CC=C3O)C4=CC=C(C=C4)C(=O)O)O'] | Inclusion Criteria: - Patients of both genders aged from 1 month up to less than 18 years at the time of enrolment - Patients affected by any hereditary haemoglobinopathy requiring chronic transfusion therapy and chelation, including but not limited to thalassemia syndromes and sickle cell disease - Patients on current treatment with deferoxamine (DFO) or DFX or DFP in a chronic transfusion program receiving at least 150 mL/kg/year of packed red blood cells (corresponding approximately to 12 transfusions); - For patients naïve to chelation treatment: patients that have received at least 150 mL/kg of packed red blood cells (corresponding to approximately 12 transfusions) in a chronic transfusion program and with serum ferritin levels ≥ 800 ng/mL; - Until availability of results from the PK Study (Study DEEP-1, EudraCT n. 2012-000658-67) for patients aged from 1 month to less than 6 years: known intolerance or contraindication to DFO; - Written informed consent and patient's informed assent, relating to his/her comprehension abilities and level of maturity Exclusion Criteria: - Patients with intolerance or known contraindication to either DFP or DFX - Patients receiving DFX at a dose > 40 mg/kg/day or DFP at a dose > 100 mg/kg/day at screening - Platelet count <100.000/mm3 during the run-in phase - Absolute neutrophils count <1.500/mm3 during the run-in phase - Hb levels lower than 8g/dL during the run-in phase - Evidence of abnormal liver function - Iron overload from causes other than transfusional haemosiderosis - Severe heart dysfunction secondary to iron overload - Serum creatinine level > ULN (Upper Limit of Normal) for age during the run-in phase - History of significant medical or psychiatric disorder - The patient has received another investigational drug within 30 days prior to this clinical trial - Fever and other signs/symptoms of infection in the 10 days before baseline assessment - Concomitant use of trivalent cation-dependent medicinal products such as aluminium-based antacids - Positive test for β-HCG (Human chorionic gonadotropin) and lactating female patients | |
| 26 | NCT04051853 | terminated | slow accrual. | 0 | phase 2 | ['bclc stage c hcc', 'cp-b liver cirrhosis'] | ["['Z52.6', 'K71.8', 'K71.7', 'A06.4', 'C22.0', 'C22.3', 'K70.0']"] | ['sorafenib'] | ['CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F'] | Inclusion Criteria: - Male or female, 18 years of age or older - Diagnosis of HCC: diagnosis based on the following criteria: 1. 1 radiologic technique: Focal lesion >1 cm with arterial hypervascularization in 4-phase CT or dynamic contrast enhanced MRI OR 2. 2 coincidental dynamic radiologic techniques (CT or MRI) in case one imaging technique is non-conclusive and lesion > 1 cm OR 3. biopsy proven HCC - Patients with advanced HCC - BCLC stage C - Cancer related symptoms (symptomatic tumors, ECOG Performance status 1-2), macrovascular invasion (either segmental or portal invasion) or extrahepatic spread (lymph node involvement or distant metastases) - Not eligible for TACE (; i.e. diffuse tumors, tumors larger than 5 cm) - Not eligible for curative resection or RFA - Patients with CP-B liver cirrhosis (CP-B score 7 or 8) - Capable of giving written informed consent - History of organ transplant (including prior liver transplantation) is allowed - HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) is allowed Exclusion Criteria: Subjects will not be enrolled in the study if any of the following criteria apply: - CP-B9 liver cirrhosis - CP-C liver cirrhosis - Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial - Concurrent antitumoral treatment for HCC or other malignancies - Not eligible for sorafenib treatment - Bilirubin > 51 micromol/L - If female, pregnant or breast feeding (females of child-bearing potential must use adequate contraception and must have a negative pregnancy test performed within 7 days prior to inclusion into this study) - If male, not using adequate birth control measures - One or more of the following: - WBC <2,500 cells/mm3, - ANC <1,500 cells/mm3, - platelets <50,000/mm3, - ECOG performance status >2 - Patients with known GFR <30 mL/min/1.73m2 - Significant cardiovascular disease; e.g., myocardial infarction within 6 months of inclusion, chronic heart failure (New York Heart Association class III or IV), unstable coronary artery disease - Uncontrolled hypertension i.e. systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mm Hg despite optimal medical management (2 classes of antihypertensive drugs) - History of hemorrhage / bleeding events of grade 3 or worse within 30 days before inclusion into this study - Previous variceal bleeding within the past 3 months Additional exclusion criteria for cocktail test - Consumption of grapefruit or grapefruit juice and/or kumquats, pummelos, exotic citrus fruit (i.e., star fruit, bitter melon) or grapefruit hybrids from seven days prior to the first dose of cocktail. - Use of herbal medicine or medication that induce or inhibit CYP3A4/5, CYP2C9, CYP2D6, CYP1A2 and CYP2C19 - Use of omeprazole, warfarin, metoprolol, caffeine or midazolam (=medication of the probe cocktail) - Concurrent anticoagulant therapy |
| 27 | NCT02720510 | terminated | a study was terminated due to low enrollment. | 0 | phase 2 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['revlimid', 'velcade', 'dexamethasone', 'farydak'] | ['C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3N', 'B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O', 'CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C', 'CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)C=CC(=O)NO'] | Key Inclusion Criteria: - Patient newly diagnosed with multiple myeloma, based on following IMWG 2014 definition (Rajkumar et al 2014): - Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: - Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder - Any one or more of the following biomarkers of malignancy: 1. Clonal bone marrow plasma cell percentage ≥ 60% 2. Involved: uninvolved serum free light chain ratio ≥ 100 3. >1 focal lesions on MRI studies - Patient with measurable disease defined by at least 1 of the following conditions present at screening: - Serum M-protein by Protein Electrophoresis (PEP) ≥ 1.0 g/dL (≥ 10 g/L). - Urine M-protein by PEP ≥ 200 mg/24 hours. Involved serum free light chain level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum free light chain ratio is abnormal. - Patient eligible for autologous stem cell transplantation based on the investigator's clinical judgment. - Patient with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 - Patient's age ≥ 18 and <75 years at time of signing the informed consent - Patient provided written informed consent prior to any screening procedures - Women of childbearing potential (WOCBP) with a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline Key Exclusion Criteria: Patients eligible for this study must not meet any of the following criteria: - Any concomitant anti-cancer therapy (other than bortezomib/lenalidomide/dexamethasone; bisphosphonates are permitted only if commenced prior to the start of screening period) - Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease). - Allogeneic stem cell transplant recipient presenting with graft versus host disease either active or requiring immunosuppression - Patient shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug, following locally applicable prescribing information - Patient with rade ≥ 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination at screening - Patient received prior treatment with DAC inhibitors including Panobinostat - Patient needing valproic acid for any medical condition during the study or within 5 days prior to first administration of panobinostat/study treatment. - Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted only if commenced prior to the start of screening period) - Patient who received: 1. prior anti-myeloma chemotherapy or medication including Immunomodulator (IMiDs) and Dex ≤ 3 weeks prior to start of study. 2. experimental therapy or biologic immunotherapy including monoclonal antibodies ≤ 4 weeks prior to start of study. 3. prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior start of study. - Patient has not recovered from all therapy-related toxicities associated with above listed treatments to < grade 2 CTCAE. - Patient undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to < grade 2 CTCAE - Patients with evidence of mucosal or internal bleeding - Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 month prior to screening) - Inability to determine the Fridericia's Correction Formula (QTc) F interval - Patient with an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection) - Sexually active males unless they use a condom during intercourse while taking the drug during treatment, and for 6 months after stopping treatment - Pregnant or nursing (lactating) women. |
| 28 | NCT02724527 | unknown status | 0 | phase 2 | ['cystic fibrosis'] | ["['E84.9', 'Z14.1', 'E84.0', 'E84.11', 'E84.8', 'E84.19', 'P09.4']"] | ['cavosonstat', 'placebo'] | ['C1=CC(=C(C=C1C(=O)O)Cl)C2=NC3=C(C=C2)C=C(C=C3)O'] | Inclusion Criteria: - Confirmed diagnosis of CF, heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) - Have been treated with chronic ivacaftor twice daily for at least 6 months prior to Screening (date of consent) and are currently being treated with commercially available Ivacaftor - Negative serum pregnancy test - Weight ≥ 40 kg at screening - Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening Exclusion Criteria: - Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment that has completed within 2 weeks of Study Day 1 or hospitalization discharge within 2 weeks of Study Day 1 - Recent infection (per investigator discretion) with organisms associated with more rapid decline in pulmonary status, for example: Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus - Any change in the regimen for chronic therapies for CF lung disease (e.g., Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1 - Blood hemoglobin < 10 g/dL at screening - Serum albumin < 2.5 g/dL at screening - Abnormal liver or renal function - History of ventricular tachycardia or other clinically significant ventricular arrhythmias - History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval (> 450 msec for men; > 470 msec for women) - History of solid organ or hematological transplantation - History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening - Use of continuous (24 hr/day) or nocturnal supplemental oxygen | |
| 29 | NCT02728700 | terminated | accrual factor | 0 | phase 1 | ['adult hodgkin lymphoma', 'adult myelodysplastic syndrome', 'blast phase chronic myelogenous leukemia, bcr-abl1 positive', 'childhood chronic myelogenous leukemia, bcr-abl1 positive', 'childhood hodgkin lymphoma', 'childhood myelodysplastic syndrome', 'chronic phase chronic myelogenous leukemia, bcr-abl1 positive', 'myelofibrosis', 'primary myelofibrosis', 'recurrent adult acute lymphoblastic leukemia', 'recurrent adult acute myeloid leukemia', 'recurrent adult non-hodgkin lymphoma', 'recurrent childhood acute lymphoblastic leukemia', 'recurrent childhood acute myeloid leukemia', 'recurrent childhood non-hodgkin lymphoma', 'recurrent chronic myelogenous leukemia, bcr-abl1 positive', 'refractory chronic myelogenous leukemia, bcr-abl1 positive', 'refractory non-hodgkin lymphoma'] | ["['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['F80.81', 'F84.3', 'F93.8', 'F93.9', 'R62.0', 'E71.520', 'F64.2']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['D46.Z', 'D46.9', 'C94.6', 'D46.C']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['D75.81', 'C94.41', 'C94.42', 'C94.40']", "['D75.81', 'C94.41', 'C94.42', 'C94.40']", "['C83.57', 'C83.50', 'C91.01', 'C91.02', 'C83.52', 'C83.56', 'C83.53']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C83.57', 'C83.50', 'C91.01', 'C91.02', 'C83.52', 'C83.56', 'C83.53']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']"] | ['mycophenolate mofetil', 'sirolimus'] | ['CC1=C2COC(=O)C2=C(C(=C1OC)CC=C(C)CCC(=O)OCCN3CCOCC3)O', 'CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)O)C)C)O)OC)C)C)C)OC'] | Inclusion Criteria: - Subjects must have one of the following disease categories: - Acute myeloid leukemia (AML) beyond 2nd remission or relapsed/refractory disease - Acute lymphoblastic leukemia (ALL) beyond 2nd remission or relapsed/refractory disease - Chronic myeloid leukemia (CML) beyond 2nd chronic phase or in blast crises - Myelodysplastic syndrome (MDS) - Myeloproliferative disorders including myeloid metaplasia and myelofibrosis - High risk non-Hodgkin's lymphoma (NHL) in first remission - Relapsed or refractory NHL - Hodgkin's lymphoma (HL) beyond first remission - Performance status by Karnofsky of >= 70% or Lansky > 70% for patients < 16 years of age - Human leukocyte antigen (HLA) mismatched related or unrelated donor identified 8/10 or 9/10 - Willingness to take oral medications during the transplantation period - Willingness and ability to sign a written informed consent (assent if applicable) Exclusion Criteria: - Prior myeloablative allogeneic or autologous HSCT - Human immunodeficiency virus (HIV) infection - Pregnant or lactating females - Evidence of uncontrolled active infection - Down syndrome - Serum creatinine (CR) < 1.5mg/dl or 24 hour CR clearance < 50 ml/min - Direct bilirubin > 2 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN - Carbon monoxide diffusing capability test (DLCO) > 60% predicted and in children- room air oxygen saturation > 92% - Left ventricular ejection fraction < 45% and in children-shortening fraction < 26% - Fasting cholesterol > 300 mg/dl or triglycerides > 300 while on lipid lowering agents - Patients who have received an investigational drug within 30 days of enrollment in study - Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ; cancer treated with curative intent > 5 years will be allowed; cancer treatment with curative intent =< 5 years will not be allowed |
| 30 | NCT02721979 | terminated | terminated due to slow accrual | 0 | phase 2 | ['prostate adenocarcinoma'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['apalutamide'] | ['CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F'] | Inclusion Criteria: - Have signed an informed consent document - Be willing/able to adhere to the prohibitions and restrictions specified in this protocol - Written authorization for use and release of health and research study information has been obtained - Life expectancy >= 10 years (as determined by the treating physician) - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 - Histologically confirmed adenocarcinoma of the prostate as documented by a minimum 12 core prostate biopsy completed within 1-year of enrollment (note: most recent prostate biopsy must have demonstrated prostatic adenocarcinoma) - Favorable risk prostate cancer as defined by: - Very low-risk: - Clinical stage T1c disease - PSA density (PSAD) < 0.15 ng/mL - Gleason score 6 - =< 2 core biopsies with =< 50% involvement of any biopsy core with cancer, or unilateral disease =< 2 core biopsies with any percentage involvement OR - Low risk: - Clinical stage =< T2a - PSA < 15 ng/mL - Gleason score 6 OR - Low-intermediate risk: - Clinical stage T1c - PSA < 15 ng/ml - Gleason 3+4 present in =< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy - Gleason 6 disease in all other cores / sites - Willing and qualified for active surveillance at Johns Hopkins or the University of Washington - Serum testosterone >= 150 ng/dL - Able to swallow the study drugs whole as a tablet - Hemoglobin >= 9.0 g/dL, (at screening), independent of transfusion and/or growth factors within 3 months prior to registration - Platelet count >= 100,000 x 10^9/uL (at screening) independent of transfusion and/or growth factors within 3 months prior to registration - Serum albumin >= 3.0 g/dL (at screening) - Glomerular filtration rate (GFR) >= 45 mL/min (at screening) - Serum potassium >= 3.5 mmol/L (at screening) - Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (at screening) (note: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 × ULN (at screening) - Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry - Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug Exclusion Criteria: - Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy) - Prior use of ARN-509 (apalutamide) - Have known allergies, hypersensitivity, or intolerance to ARN-509 (apalutamide) or its excipients - Prior or ongoing systemic therapy for prostate cancer including, but not limited to: - Hormonal therapy (e.g. leuprolide, goserelin, triptorelin) - Cytochrome P450 (CYP)-17 inhibitors (e.g. abiraterone, ketoconazole) - Antiandrogens (e.g. bicalutamide, nilutamide) - Second generation antiandrogens (e.g. enzalutamide) - Immunotherapy (e.g. sipuleucel-T, ipilimumab) - Chemotherapy (e.g. docetaxel, cabazitaxel) - Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements - History of any of the following: - Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to registration, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect) - Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration - Any condition that in the opinion of the investigator, would preclude participation in this study - Current evidence of any of the following: - Uncontrolled hypertension - Gastrointestinal disorder affecting absorption - Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated - Any condition that in the opinion of the investigator, would preclude participation in this study - The use of drugs known to lower the seizure threshold, including: atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone), bupropion, lithium, meperidine, pethidine, phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine), and tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine) - The use of strong CYP3A4 inhibitors, including: itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice (or grapefruits) - Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide - Strong CYP3A4 inducers, including: phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, efavirenz, tipranavir, St. John's wort **Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide - Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule |
| 31 | NCT02727751 | completed | 1 | phase 3 | ['constipation predominant irritable bowel syndrome'] | ["['K59.00', 'K59.09', 'K59.01', 'K59.02', 'K59.03', 'K59.04', 'K58.1']"] | ['tenapanor'] | ['CN1CC(C2=C(C1)C(=CC(=C2)Cl)Cl)C3=CC(=CC=C3)S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)C4=CC=CC(=C4)C5CN(CC6=C5C=C(C=C6Cl)Cl)C'] | Inclusion Criteria: - Subjects completed all 16 weeks of TEN-01-301 or all 26 weeks of TEN-01-302 - Subject demonstrated adequate compliance with the study procedures during either the TEN-01-301 or TEN-01-302 studies - Females must be of non-childbearing potential; If of child-bearing potential, must have negative pregnancy test and confirm the use of one of the appropriate means of contraception - Males must agree to use appropriate methods of barrier contraception or have documented surgical sterilization Exclusion Criteria: - Subject has been withdrawn or discontinued prematurely from either TEN-01-301 or TEN-01-302 - The subject reports using any prohibited medication and is not willing to abide by the restrictions for intake - Pregnant or lactating women | |
| 32 | NCT02723006 | terminated | business decision: protocol efficacy futility met | 0 | phase 1 | ['melanoma'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['tak-580', 'tak-202', 'vedolizumab', 'nivolumab', 'ipilimumab'] | ['CC(C1=NC=C(S1)C(=O)NC2=NC=C(C(=C2)C(F)(F)F)Cl)NC(=O)C3=C(C(=NC=N3)N)Cl'] | Inclusion Criteria: 1. Is a male or female participant of 18 years or older. 2. Has histologically confirmed, unresectable Stage III or Stage IV melanoma per the American Joint Committee on Cancer (AJCC) staging system. 3. Has an eastern cooperative oncology group (ECOG) performance status of 0-1. 4. Adequate bone marrow reserve and renal and hepatic function within 28 days before the first dose of study drug on the basis of the defined laboratory parameters. 5. For TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only: Had disease accessible for repeat nonsignificant risk biopsy (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures extending beyond the esophagus, stomach, or bowel) and willingness to undergo serial tumor biopsies. 6. Additional Inclusion Requirements for TAK-580 + nivolumab a) BRAF V600 mutation-positive or NRAS mutation-positive disease previously untreated with RAF, MEK, or other inhibitors of the mitogen-activated protein kinase (MAPK) pathway. Participants who have progressed on these agents can still be enrolled in TAK-202 (plozalizumab) + nivolumab or vedolizumab + nivolumab + ipilimumab. 7. Additional Inclusion Requirements for expansion cohorts only a) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1) and at least 1 nonsignificant risk, non-target lesion accessible for biopsy per the guidelines above (for TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only). Exclusion Criteria: 1. Has active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (greater than [>] 10 milligram per day [mg/day] prednisone equivalents) for at least 2 weeks prior to study drug administration. 2. Completed a prior therapy less than (<) 2 weeks prior to first dose and for whom adverse events (AEs) related to prior therapy had not returned to baseline or improved to Grade 1. 3. Has active, known or suspected autoimmune disease. 4. Has a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. 5. Has a history of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis (including pneumonitis), interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted. 6. Is previously diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B or C. 7. Additional Exclusion Requirements for arm 1 only (nivolumab Plus TAK-580) 1. Concomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580. 2. Treatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580. 3. Left ventricular ejection fraction (LVEF) <50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug. 4. Known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of the TAK-580. 8. Additional Exclusion Requirements for arm 3 only (vedolizumab Plus nivolumab Plus ipilimumab) 1. Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab. 2. Has a history of any major neurological disorders, including stroke, multiple sclerosis, or neurodegenerative disease. 3. Has taken any live vaccinations within 30 days before study drug administration except for the influenza vaccine. |
| 33 | NCT02726074 | completed | 1 | phase 4 | ['epilepsy'] | ["['G40.803', 'G40.804', 'G40.911', 'G40.919', 'G40.B11', 'G40.B19', 'G40.801']"] | ['perampanel'] | ['C1=CC=C(C=C1)N2C=C(C=C(C2=O)C3=CC=CC=C3C#N)C4=CC=CC=N4'] | Inclusion Criteria: - Have a diagnosis of epilepsy with partial onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981) - Need an initial add-on therapy after failure to control seizures with the first or further monotherapy at the optimal dose and duration - Despite antiepileptic drug (AED) treatment within the last 8 weeks, participants must have had greater than or equal to 2 partial onset seizures, and the interval between those seizures should be more than 24 hours prior to Visit 1 (Week 0). - Are currently being treated with stable doses of monotherapy for 8 weeks prior to Visit 1 (Week 0) (Standard AEDs) - If antidepressants or antianxiety drugs are used, participants must be receiving stable doses and administrations of antidepressants or antianxiety drugs for 8 weeks prior to Visit 1 (Week 0) Exclusion Criteria: - Females who are pregnant (positive beta-human chorionic gonadotropin (β-hCG test) or breastfeeding - Presence of previous history of Lennox-Gastaut syndrome - Presence of nonmotor simple partial seizures only - Presence of primary generalized epilepsies or seizures such as absences and/or myoclonic epilepsies - A history of status epilepticus within 12 weeks before Visit 1 (Week 0) - Participants on antipsychotics or who have psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of attempted suicide within 1 year before Visit 1 (Week 0) - Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors - Concomitant use of barbiturates (except for seizure control indication and premedication for electroencephalogram [EEG]) and benzodiazepines (except for seizure control indication) within 8 weeks prior to Visit 1 (Week 0) - Use of intermittent rescue benzodiazepines (that is, 1 to 2 doses over a 24-hr period considered one-time rescue) 2 or more times in an 8-week period prior to Visit 1 (Week 0) - Participant who is participating in other intervention clinical trial | |
| 34 | NCT02729909 | completed | 1 | phase 3 | ['constipation'] | ["['K59.00', 'K59.09', 'K59.01', 'K59.02', 'K59.03', 'K59.04', 'K58.1']"] | ['lubiprostone', 'placebo'] | ['CCCCC(C1(CCC2C(O1)CC(=O)C2CCCCCCC(=O)O)O)(F)F'] | Inclusion Criteria: 1. In the opinion of the investigator, is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Has a history of constipation defined as having spontaneous bowel movement (SBM) frequency of less than 3 times per week on average for 6 months or longer and for whom the same SBM frequency is observed during the Screening Period. 4. Has had 1 or more of the symptoms associated with SBM (described below) for 6months or longer at the start of Screening: 1. Scybalum stool or hard feces in at least 1 out of every 4 bowel movements. 2. Sensation of incomplete evacuation in at least 1 out of every 4 bowel movements. 3. Straining in at least 1 out of every 4 bowel movements. 5. Rarely has loose stools without the use of laxatives. 6. Is willing and able to keep a diary on his/her own and willing and able to complete a questionnaire. 7. Is male or female and aged 18 years or older, at the time of signing an informed consent. 8. A female participant of childbearing potential who is sexually active agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and 14 days after the last dose of study drug. Exclusion Criteria: 1. Has received any investigational compound within 30 days prior to Screening. 2. Has received lubiprostone in a previous clinical study or as a therapeutic agent. 3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 4. Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening. 5. Has a history or clinical manifestations of significant mechanical obstruction (intestinal obstruction due to tumor, hernia etc). 6. Has a history of hypersensitivity or allergies to lubiprostone or any of its excipients. 7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening Visit. 8. Is required to take excluded medications. 9. If female, is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. 10. Participant whose constipation is considered to be due to drugs or to whom a prohibited concomitant medication has been administered. 11. Is having chronic constipation due to a secondary cause (medications, diabetes mellitus, hypothyroidism, depression, etc.) 12. Has sufficient criteria for irritable bowel syndrome (IBS) or functional defecation disorder. 13. SBM frequency is 3 or more per week. 14. SBM frequency has been less than 3 times per week for less than 6 months in duration or whose symptoms associated with SBM have been present for less than 6 months (hard feces, sensation of incomplete evacuation, or straining). 15. Has received treatment with a rescue medication within 24 hours prior to the first dose on the morning of Day1: bisacodyl suppository, which is a standard laxative, glycerin enema, or any other rescue medication. 16. Has megacolon/megarectum or has received a diagnosis of intestinal pseudo-obstruction. 17. Has confirmed or suspected organic disorders of the large intestine (obstruction, stenosis, carcinoma, or inflammatory bowel disease). Organic disorders of the large intestine can be confirmed or ruled out using the results of enema X-ray examination or total colonoscopy performed in the previous 2 years. If the participant has no history or shows no current evidence of weight loss, anemia, or rectal bleeding, organic disorders may be ruled out based on the results of such testing performed in the past 3 years. Any participant in whom total colonoscopy has detected a polyp requiring treatment is excluded from this study .Note: Participant should not be screened unless at least 7 days have passed since an enema X-ray examination, total colonoscopy or sigmoidoscopy have been performed. 18. Has been hospitalized for gastrointestinal or abdominal surgery within 3 months prior to Screening. 19. Has a significant cardiovascular, liver, lung, kidney, neurological, or mental disease (including existing alcohol or drug abuse problem) or a systemic disease. 20. Has significant clinical findings or in whom a significant abnormality has been found in hematology test, serum chemistry, or urinalysis. 21. Participant in whom noncompliance with the study protocol (administration schedule, visit schedule, diary completion or other study procedure) is expected. 22. Has a history of malignant disease (except basal cell carcinoma) within 5 years prior to Screening. 23. Has any screening abnormal laboratory value that suggests a clinically significant underlying disease or condition that may prevent the participant from entering the study; or the participant has: creatinine >1.5 mg/dL, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN), or total bilirubin >2.0 mg/dL with AST/ALT elevated above the limits of normal values. 24. Participant who the investigator/subinvestigator has determined ineligible to participate in this study for any reason other than the above. | |
| 35 | NCT02721459 | active, not recruiting | 0 | phase 1 | ['melanoma', 'skin cancer'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']", "['C79.2', 'C44.500', 'C44.90', 'D23.9', 'D48.5', 'C44.00', 'C44.301']"] | ['xl888', 'vemurafenib', 'cobimetinib'] | ['CCC(C)NC1=C(C=C(C(=C1)C(=O)NC2CC3CCC(C2)N3C4=NC=C(C=C4)C(=O)C5CC5)C)C(=O)N', 'CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(C=C4)Cl)F', 'C1CCNC(C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O'] | Inclusion Criteria: - Must be 18 years of age or above. All races and ethnicities are eligible and no upper limit of age is specified. - Must have cytologically or histologically-confirmed unresectable melanoma that harbors a BRAF V600 mutation determined by pyrosequencing assay or equivalent genotyping assay in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, meeting one of the following AJCC staging criteria: 1.) American Joint Committee on Cancer (AJCC) stage IV (Tany, Nany, M1a, b, or c); 2.) AJCC stage IIIB or IIIC with unresectable nodal/locoregional involvement. - Adequate hepatic, renal, and bone marrow function with parameters obtained within 4 weeks prior to initiation of study treatment. - Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. - Willing to give written informed consent per institutional guidelines and must be able to adhere to dose and visit schedules. - Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥1 year. - Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. - Treatment-naïve and previously treated patients will be included; however, patients may not have received a BRAF, Mitogen Activated Kinase (MEK) or HSP90 inhibitor in the past. - May have received prior systemic and/or radiation therapy. All adverse events associated with prior systemic therapy or radiation therapy must have resolved to ≤ Grade 1 prior to start of study. - Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Exclusion Criteria: - Women who are pregnant, intend to become pregnant or are nursing. - Previously treated with BRAF, MEK or HSP90 inhibitor therapy. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. - HIV-positive patients on combination antiretroviral therapy. - Potential participants with untreated or uncontrolled brain metastases or evidence of leptomeningeal disease. Patients with asymptomatic brain metastases or previously treated brain metastases that are stable (i.e., not requiring corticosteroids) at the time of study start will be eligible. - Previous malignancy is not an exclusion provided that the other malignancy is considered under control, patient is not on concomitant anti-cancer drug therapy, and target lesions from melanoma are clearly defined for response assessment. - History of malabsorption or other condition that would interfere with absorption of study drugs. - The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment: St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer); Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor). - Ocular: History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration. - Cardiac: History of clinically significant cardiac dysfunction. | |
| 36 | NCT02723578 | completed | 0 | phase 2 | ['metastatic colorectal cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['pemetrexed', 'erlotinib'] | ['C1=CC(=CC=C1CCC2=CNC3=C2C(=O)NC(=N3)N)C(=O)NC(CCC(=O)O)C(=O)O', 'COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC'] | Inclusion Criteria: 1. Male or female, aged ≥ 19 years 2. Histologic or cytologic confirmed diagnosis of colorectal carcinoma with metastatic (STAGE IV) disease. 3. Confirmed KRAS(codon 12 or 13) status 4. Prior chemotherapy for metastatic disease is required; prior regimens must include fluoropyrimidine, oxaliplatin and irinotecan 5. Eastern Cooperative Oncology Group performance status ≤ 2 6. Patients who can swallow oral medication. 7. Life expectancy of greater than 3 months 8. Patients must have normal organ and marrow function as defined below: - absolute neutrophil count ≥ 1,500/mm3 - hemoglobin ≥ 9 g/dl - platelets ≥ 100,000/mm3 - serum total bilirubin ≤ 1.5 X institutional upper limit of normal - aspartate aminotransferase(SGOT)/alanine aminotransferase(SGPT) ≤ 3.0 X institutional upper limit of normal (≤ 5 times the upper institutional limits of normal if hepatic metastases are present) - serum creatinine ≤ 1.5 times the institutional upper limits of normal or Creatinine Clearance ≥ 50ml/min 9. The effects of Pemetrexed and Erlotinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception (hormonal or barrier method of birth control; abstinence) during the study and for 6 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 10. Participant is willing and able to give informed consent for participation in the study. Voluntary signed and dated written informed consent form in accordance with regulatory and institutional guidelines obtained before the performance of any protocol-related procedures not part of normal patient care. Exclusion Criteria: 1. Previous treatment with Pemetrexed and Erlotinib 2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pemetrexed or Erlotinib or other agents used in the study 3. Patients who can not allow the administration of Folic acid or Vitamin B12. 4. Past or current history of neoplasm other than colorectal carcinoma with a disease-free interval of less than 5 years, except for non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix. 5. Systemic chemotherapy within three weeks after the administration of the last before the test treatment 6. Major surgical operation or major trauma within 4 weeks. 7. Patients who have had wide-ranged radiotherapy within 4 weeks or limited radiotherapy within 2 2 weeks. 8. Persistent toxicity (> CTCAE grade 1) related to previous treatment except for the hair loss. 9. Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. 10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 11. Breast-feeding or pregnant female | |
| 37 | NCT02722369 | terminated | low recruitment, lack of efficacy and increased adverse events in investigational arm. | 0 | phase 2 | ['small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['gemcitabine', 'carboplatin', 'etoposide', 'hydroxychloroquine'] | ['C1=CN(C(=O)N=C1N)C2C(C(C(O2)CO)O)(F)F', 'C1CC(C1)(C(=O)O)C(=O)O.[NH2-].[NH2-].[Pt+2]', 'CC1OCC2C(O1)C(C(C(O2)OC3C4COC(=O)C4C(C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O', 'CCN(CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl)CCO'] | Inclusion Criteria: - Histologically or cytologically confirmed SCLC - Stage IV disease - Performance status ECOG 0-2 - Life expectancy >8 weeks - Age 18 or over - Willing and able to give informed consent - Patient considered able to tolerate chemotherapy - Adequate renal function - defined by GFR ≥50mL/min as measured by EDTA or C&G - Adequate bone marrow reserve: Absolute neutrophil count ≥1.5 x 109/L, haemoglobin ≥90 g/L, platelet count ≥100 x 109/L - Negative pregnancy test for WCBP - Highly effective contraception is mandatory for all patients of reproductive potential - At least one site of measurable disease (target lesion) for RECIST 1.1 evaluation - Hypersensitivity or history of severe allergic reaction to any of the IMPs - Able to swallow medication Exclusion Criteria: - Mixed cell histology (i.e. NSCLC and SCLC) - Prior macular degeneration or diabetic retinopathy - History of glaucoma - Patients with abnormal LFTs (ALP, ALT/AST*) that are ≥3 x ULN (≥5 x ULN for patients with liver metastases) - Patients with abnormal bilirubin levels that are ≥1.5 x ULN - Prior treatment for this disease e.g. chemotherapy, surgery, radiotherapy (except palliative radiotherapy to bone metastases) - Documented side effects to chloroquine or related agents - Treatment with chloroquine or related agents within the last year prior to randomisation - Evidence of significant medical condition or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial - Previous medical history of prolonged QT interval - A history of prior malignant tumour, unless the patient has been without evidence of disease for at least 3 years or the tumour was a non-melanoma skin tumour or early cervical cancer - Patients with symptomatic brain metastases - Women who are breastfeeding - Concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs e.g. phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine - Patients who are unable to have their digoxin levels regularly monitored - if both ALT and AST performed then both need to be recorded |
| 38 | NCT02721433 | completed | 1 | phase 4 | ['breast cancer', 'prostate cancer', 'metastasis'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['pamidronate', 'denosumab', 'zoledronate'] | ['C(CN)C(O)(P(=O)(O)O)P(=O)(O)O', 'C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O'] | Inclusion Criteria: - Patients with either radiologically and/or histologically confirmed bone metastases from castrate resistant prostate cancer (36) or breast cancer. - About to start or currently receiving BTA therapy. - Serum creatinine >30 ml/min and corrected serum calcium ≥ 2 mmol/l - Age ≥ 18 years. - Able to provide verbal consent Exclusion Criteria: - For CRPC patients - Definite contraindication for denosumab at baseline (e.g. hypocalcaemia [Albumin-corrected serum calcium < 2.0 mmol/l]). - History of or current evidence of osteonecrosis of the jaw. - Radiotherapy or surgery to the bone planned within 4 weeks after randomization. - Known hypersensitivity to trial drug or hypersensitivity to any other component of the trial drug (e.g. fructose). - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol. | |
| 39 | NCT02720523 | completed | 1 | phase 2/phase 3 | ['rheumatoid arthritis'] | ["['M06.9', 'M05.9', 'M06.08', 'M06.00', 'M06.011', 'M06.012', 'M06.019']"] | ['placebo', 'upadacitinib'] | ['CCC1CN(CC1C2=CN=C3N2C4=C(NC=C4)N=C3)C(=O)NCC(F)(F)F'] | Inclusion Criteria: - Diagnosis of rheumatoid arthritis (RA) for >= 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA. - Subjects have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy >= 3 months and on a stable dose for >= 4 weeks prior to the first dose of study drug. - Subject has >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. - Subjects with prior exposure to at most one biological disease-modifying anti-rheumatic drug (bDMARD) may be enrolled (up to 20% of total number of subjects) after the required washout period. Specifically, prior to enrollment: 1. Subjects with limited exposure to bDMARD (< 3 months) OR 2. Subjects who are responding to bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration). Exclusion Criteria: - Prior exposure to any Janus kinase (JAK) inhibitor - Subjects who are considered inadequate responders (lack of efficacy) to bDMARD therapy, after minimum 3 months treatment, as determined by the Investigator. - History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis [SpA] including ankylosing spondylitis and non-radiographic axial SpA, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]). Current diagnosis of secondary Sjogren's Syndrome is permitted. | |
| 40 | NCT02726399 | terminated | low accrual rate | 0 | phase 2 | ['gastric cancer', 'gastroesophageal junction cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C19', 'D12.7', 'Z85.048']"] | ['ramucirumab', 'trastuzumab', 'capecitabine', 'cisplatin'] | ['CCCCCOC(=O)NC1=NC(=O)N(C=C1F)C2C(C(C(O2)C)O)O', 'N.N.Cl[Pt]Cl'] | Inclusion Criteria: - Patients must have pathologically or cytologically MSKCC confirmed diagnosis of gastric or GEJ adenocarcinoma. - Patients must have Stage IV gastric or GEJ adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:CEP17 ratio ≥ 2.0). MSKCC confirmation of HER2 status is not mandatory prior to enrollment and treatment on study. For patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC for purpose of analysis and will not impact the patient's eligibility. - Available archival tumor tissue should be submitted to MSKCC for IMPACT analysis, but will not be required prior to registration. Note: if tissue is depleted, patient will still be eligible after discussion with the PI. - Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease per RECIST 1.1. - Patients may have received no prior chemotherapy for Stage IV disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration. - Age of 18 years or older. - ECOG performance status 0-1. - Peripheral neuropathy ≤ grade 1 - Patients who have adequate hepatic function as defined by a total bilirubin ≤1.5 times upper limit of institutional normal value (ULN) mg/dL (except patients with Gilbert's disease), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times ULN or ≤ 5.0 times the ULN in the setting of liver metastases. - Patients who have adequate hematologic function, as evidenced by absolute neutrophil count (ANC) ≥1500/μL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/μL. - Patients who have adequate renal function as defined by calculated creatinine clearance ≥60 mL/minute using the Cockcroft-Gaul formula or equivalent method. - Patients whose urinary protein is ≤2+ on routine urinalysis (UA; if routine analysis is >2+, a 24-hour urine collection for protein must demonstrate <2g of protein in 24 hours to allow participation in this protocol). - The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy. - Patients, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). - Female patients of childbearing potential must have a negative serum pregnancy test within 7 days of study entry. Exclusion Criteria: - Patients who have uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or >100 mmHg diastolic for >4 weeks) despite standard medical management. - Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating gastric/GEJ cancer. Previously received trastuzumab as part of a regimen in the metastatic setting with evidence of progression. 89Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted. - Patients having: - Cirrhosis at a level of Child-Pugh B (or worse) or - Cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis. - Active or clinically significant cardiac disease including: - Congestive heart failure - New York Heart Association (NYHA) > Class II. - Active coronary artery disease. - Left ventricular function <50%. - Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. - Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization. - Patients who have experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment. - Patients who are receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-infalmmatory drugs (NSAIDs, inluding ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin (maximum dose 325 mg/day is permitted. - Evidence or history of bleeding diathesis or coagulopathy. - Patients who have experienced any Grade 3-4 GI bleeding within 3 months prior to enrolment. - Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study. - Patients with prior trastuzumab treatment. - Patients with known active brain or central nervous system metastases, including leptomeningeal disease. Patients with treated and asymptomatic brain metastases may be eligible after discussion with PI. - Patients who are pregnant or breast-feeding. - Patients with a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment. - The patient has undergone major surgery within 28 days prior to first dose of protocol therapy - Patients may not have had major surgical procedure within 2 weeks of registration. - Patients who have elective or planned major surgery to be performed during the course of the clinical trial.Minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy is permitted. - Patients may not have had radiation within 28 days prior to first dose weeks of registration. - Patients may not have any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial. |
| 41 | NCT02729051 | completed | 1 | phase 3 | ['pulmonary disease, chronic obstructive'] | ["['J44.9', 'J44.1', 'J44.0']"] | ['ff/umec/vi', 'ff/vi', 'umec', 'placebo', 'albuterol/salbutamol'] | ['Status: 400', 'Status: 400', 'C1C[N+]2(CCC1(CC2)C(C3=CC=CC=C3)(C4=CC=CC=C4)O)CCOCC5=CC=CC=C5.[Br-]', 'Status: 503', 'Status: 400'] | Inclusion Criteria: Informed Consent: A signed and dated written informed consent prior to study participation. - Type of subject: Outsubject. - Age: Subjects 40 years of age or older at Screening (Visit 1). - Gender: Male or female subjects. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: - Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. - Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study treatmentand until after the last dose of study treatmentand completion of the follow-up visit. - COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society. - Smoking History: Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at Screening (Visit 1) [number of pack years = (number of cigarettes per day divided by 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (Visit 1). Note: Pipe and/or cigar use cannot be used to calculate pack-year history. - Severity of COPD symptoms: A score of >=10 on the COPD Assessment Test (CAT) at Screening (Visit1). - Severity of COPD Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 at Screening (Visit 1). - Existing COPD maintenance treatment: Subject must be receiving daily maintenance treatment for their COPD for at least 3 months prior to Screening (Visit 1). Note: Subjects receiving only as needed COPD medications are not eligible. - History of Exacerbations: Subjects must demonstrate: a post-bronchodilator FEV1 <50 percent predicted normal at Screening (Visit 1) and a documented history of >=1 moderate or severe COPD exacerbation in the 12 months prior to Screening or a post-bronchodilator 50 percent =< FEV1 <80 percent predicted normal at Screening (Visit 1) and a documented history of >=2 moderate exacerbations or a documented history of >=1 severe COPD exacerbation (hospitalised) in the 12 months prior to Screening (Visit 1). Notes: Percent predicted will be calculated using the European Respiratory Society Global Lung Function Initiative reference equations; A documented history of a COPD exacerbation (e.g., medical record verification) is a medical record of worsening COPD symptoms that required systemic/oral corticosteroids and/or antibiotics (for a moderate exacerbation) or hospitalisation (for a severe exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnoea, sputum volume, or sputum purulence (colour). Subject verbal reports are not acceptable. - French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Exclusion Criteria: - Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study. - Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD, which is the primary cause of their respiratory symptoms). - Alpha 1-antitrypsin deficiency: Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD. - Other respiratory disorders: Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders (e.g. clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are excluded if these conditions are the primary cause of their respiratory symptoms. - Lung resection: Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening (Visit 1). - Risk Factors for Pneumonia: immune suppression (e.g. advanced human immune deficiency virus (HIV) with high viral load and low cluster of differentiation 4 (CD4) count, Lupus on immunosuppressants that would increase risk of pneumonia) or other risk factors for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis). Notes: Subjects at a high risk for pneumonia (e.g. very low body mass index (BMI), severely malnourished or very low FEV1) will only be included at the discretion of the investigator. - Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening (Visit 1) and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable). - Other Respiratory tract infections that have not resolved at least 7 days prior to Screening (Visit 1). - Abnormal Chest x-ray: Chest x-ray reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD, or another condition that would hinder the ability to detect an infiltrate on chest x-ray (e.g. significant cardiomegaly, pleural effusion or scarring). All subjects will have a chest x-ray at Screening (Visit 1) [or historical radiograph or computerised tomography (CT) scan obtained within 3 months prior to Screening (Visit 1). Notes: Subjects who have experienced pneumonia and/or moderate or severe COPD exacerbation within 3 months of Screening (Visit 1) must provide a post pneumonia/exacerbation chest x-ray or have a chest x-ray conducted at Screening (Visit 1); For sites in Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is not available, approval to conduct a diagnostic chest x-ray will need to be obtained from the Federal Office for Radiation Protection (BFS). - Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. - Unstable liver disease: ALT >2 times upper limit of normal (ULN); and bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent). Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Notes: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis; Chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria. - Unstable or life threatening cardiac disease: subjects with any of the following at Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the last 6 months; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class 4 Heart failure. - Abnormal and clinically significant 12-Lead ECG finding: Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding that would preclude a subject from entering the trial is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following: atrial fibrillation (AF) with rapid ventricular rate >120 beats per minute (BPM); sustained or nonsustained ventricular tachycardia (VT); Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted). - Contraindications: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator contraindicates study participation. - Cancer: Subjects with carcinoma that has not been in complete remission for at least 3 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 3 year waiting period if the subject has been considered cured by treatment. - Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy >3 Liters per minute (Oxygen use <= 3 Liters/minute flow is not exclusionary.) - Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol for the 4-hour period required prior to spirometry testing at each study visit. - Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years. - Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits. - Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study. - Affiliation with investigator site: Study investigators, sub-investigators, and study coordinators, employees of a participating investigator or study site, or immediate family members of the aforementioned that is involved with this study. - Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete study related materials. - Medication prior to Screening: Use of the following medications within 30 days prior to Screening (Visit 1) or requirement for their use during the study: Use of long term continuous antibiotic therapy; systemic, oral, parenteral corticosteroids (Intra-spinal and intra-articular injections are allowed); use of any other investigational drug: within 30 days or 5 half lives whichever is longer. | |
| 42 | NCT02513550 | completed | 1 | phase 3 | ['plaque psoriasis'] | ["['L40.0', 'L40.4', 'L40.8', 'L40.9', 'L40.1', 'L40.50']"] | ['ixekizumab', 'placebo'] | ['Status: 503'] | Inclusion Criteria: - Present with chronic plaque psoriasis for at least 6 months prior to enrollment - At least 10% BSA of psoriasis at screening and at enrollment - sPGA score of at least 3 and PASI score of at least 12 at screening and at enrollment - Candidates for phototherapy and/or systemic therapy - Participant must agree to use reliable method of birth control during the study; women must continue using birth control for at least 12 weeks after stopping treatment Exclusion Criteria: - Predominant pattern of pustular, erythrodermic, or guttate forms of psoriasis - History of drug-induced psoriasis - Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to enrollment and during the study - Received systemic non-biologic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to enrollment - Concurrent or recent use of any biologic agent - Have participated in any study with ixekizumab - Received a live vaccination within 12 weeks prior to enrollment - Serious disorder or illness other than psoriasis - Ongoing or serious infection within the last 12 weeks or evidence of tuberculosis - Major surgery within 8 weeks of baseline, or will require surgery during the study - Breastfeeding or nursing (lactating) women | |
| 43 | NCT02513160 | completed | 1 | phase 3 | ['persistent asthma'] | ["['J45.30', 'J45.40', 'J45.50', 'J45.31', 'J45.32', 'J45.41', 'J45.42']"] | ['beclomethasone dipropionate 640', 'placebo', 'beclomethasone dipropionate via 320 mcg bai', 'albuterol/salbutamol', 'beclomethasone dipropionate via 320 mcg mdi'] | ['Status: 400'] | Inclusion Criteria: - The patient has a diagnosis of asthma as defined by the NIH. The asthma diagnosis - has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in medication) for at least 30 days. - The patient has been maintained on stable doses of : - non-corticosteroid therapy - inhaled corticosteroid therapy - Written informed consent/assent is obtained. For adult patients (18 years of age and older, or as applicable per local regulations), the written informed consent form (ICF) must be signed and dated by the patient before conducting any study-related procedure. For minor patients (ages 12 to 17 years, or as applicable per local regulations), the written ICF must be signed and dated by the parent/legal guardian and the written informed assent form must be signed and dated by the patient before conducting any study-related procedure. - The patient is a male or female 12 years of age or older as of the visit when informed consent/assent is signed (screening or prescreening visit, as applicable). (Note: Age requirements are as specified or allowed by local regulations.) - The patient is able to perform acceptable and repeatable spirometry - The patient is able to use an electronic diary after training. - The patient is able to use devices properly - If female, patient is currently not pregnant, not breast feeding, nor attempting to become pregnant (for 30 days before the screening visit (SV) and throughout the duration of the study and for 30 days after patient's last study visit) or, is of childbearing potential and not sexually active, has a negative urine pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control - If male, the patient is willing to commit to an acceptable method of birth control for the duration of the study, is surgically sterile or exclusively has same-sex partner(s). - The patient does not have any concomitant conditions or treatments that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the study as judged by the investigator. - The patient/parent/legal guardian is capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements (eg, dose schedules, visit schedules, procedures, and record keeping). - The patient, as judged by the investigator, is able to discontinue all asthma medications at the SV. - other criteria apply, please contact the investigator for more information Exclusion Criteria - Life-threatening asthma, defined as a history of asthma episode(s) requiring intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures, asthma-related syncopal episode(s), or hospitalizations within the past year. - The patient received systemic corticosteroids within 30 days before the SV (for asthma exacerbation or for other indications). - The patient has participated in any investigational drug study as a randomized patient within the 30 days (starting at the final visit of that study) preceding SV (or prescreening visit, as applicable), or plans to participate in another investigational drug study at any time during this study. - The patient has previously participated in a beclomethasone dipropionate breath-actuated inhaler (device) (BAI) study as a randomized patient. - The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation. - The patient has been treated with any known strong cytochrome inhibitors during the study. - The patient has been treated with any of the prohibited medications during the prescribed (per protocol) withdrawal periods before the SV. - The patient currently smokes or has a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient may not have used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco). - The patient has a suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the SV. - The patient has a history of alcohol or drug abuse within 2 years preceding SV. - The patient has had an asthma exacerbation requiring oral corticosteroids within 1 month before the SV, or has had any hospitalization for asthma within 3 months before SV. - The patient has initiated immunotherapy (administered by any route) less than 90 days before the SV or had a dose escalation of immunotherapy less than 30 days before the SV. - The patient is unable to tolerate or unwilling to comply with the required washout periods and withholding of all applicable medications. - The patient has untreated oral candidiasis at SV. Patients with clinical visual evidence of oral candidiasis and who agree to receive treatment and comply with appropriate medical monitoring may enter the study. - The patient is either an employee or an immediate relative of an employee of the clinical investigational center. - A member of the patient's household is participating in the study at the same time. (However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened). - The patient has a disease/condition that, in the medical judgment of the investigator, would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study. - other criteria apply, please contact the investigator for more information | |
| 44 | NCT02510599 | completed | 0 | phase 2 | ['nonalcoholic steatohepatitis'] | ["['K75.81']"] | ['solithromycin'] | ['CCC1C2(C(C(C(=O)C(CC(C(C(C(=O)C(C(=O)O1)(C)F)C)OC3C(C(CC(O3)C)N(C)C)O)(C)OC)C)C)N(C(=O)O2)CCCCN4C=C(N=N4)C5=CC(=CC=C5)N)C'] | Inclusion Criteria: - Histologic evidence of NASH based on liver biopsy obtained within 180 days - NAS> or = 5 - Able to swallow capsules intact Exclusion Criteria: - Symptoms of acute liver disease - Cirrhosis on liver biopsy - Positive HIV or Hepatitis tests - Primary Biliary Cirrhosis - Poorly controlled diabetes with HgA1C >8.5% - ALT >4-fold upper limit of normal - QTcF >450 msec - CrCl <40 mL/min | |
| 45 | NCT02517021 | completed | 1 | phase 3 | ['chemotherapy-induced nausea and vomiting'] | ["['D61.810']"] | ['pro-netupitant/palonosetron', 'netupitant/palonosetron', 'dexamethasone'] | ['Status: 400', 'CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C'] | Inclusion Criteria: Cycle 1 - Signed written informed consent - Histologically or cytologically confirmed solid tumor malignancy. - Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted. - Scheduled to receive at least 4 repeated consecutive cycles of the following highly emetogenic reference chemotherapies (HEC), alone or in combination with other chemotherapeutic agents on Day 1: cisplatin administered as a single IV dose of ≥ 70 mg/m2; cyclophosphamide ≥1500 mg/m2; carmustine (BCNU) >250mg/m2; dacarbazine (DTIC); mechloretamine (nitrogen mustard) - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 . - If a patient is female, she shall be of non-childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test. - Hematologic and metabolic status adequate for receiving an highly emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance) - Able to read, understand, follow the study procedure and complete patient diary. Cycles 2 to 4: The following inclusion criteria must be checked prior to inclusion at each repeated cycle: - Participation in the study during the next cycle of chemotherapy is considered appropriate by the Investigator and does not pose unwarranted risk to the patient. - Scheduled to receive the same chemotherapy regimen as Cycle 1 or one of the reference chemotherapies as defined in Inclusion criterion 5 for Cycle 1. - If a patient is female, she shall be of non--childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test. - Adequate hematologic and metabolic status according to the Investigator's opinion. Exclusion Criteria: Cycle 1 - Lactating woman. - Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient. - Current use of illicit drugs or current evidence of alcohol abuse. - Scheduled to receive moderately or highly emetogenic chemotherapies from Day 2 to Day 5. - Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on Day 1 or between Days 1 to 5. - Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of the reference chemotherapy administration on Day 1. - Symptomatic primary or metastatic CNS malignancy. - Known hypersensitivity or contraindication to 5-HT3 receptor antagonists, to dexamethasone or to NK-1 receptor antagonists. - Known contraindication to the IV administration of 50 mL 5% glucose solution. - Previously received an NK-1 receptor antagonist. - Participation in a previous clinical trial involving IV pro-netupitant or oral netupitant administered alone or in combination with palonosetron. - Any investigational drugs (other than those given in this study) taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug during the present study. - Systemic corticosteroid therapy at any dose within 72 hours prior to the start of reference chemotherapy administration on Day 1. Topical and inhaled corticosteroids are permitted. - Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy. - Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1 week prior to Day 1. - Scheduled to receive any of the following CYP3A4 substrates within 1 week prior to Day 1: terfenadine, cisapride, astemizole, pimozide. - Received within 4 weeks prior to Day 1 or scheduled to receive any CYP3A4 inducer. - Any medication with known or potential antiemetic activity within 24 hours prior to the start of reference chemotherapy administration on Day 1 of Cycle 1, including but not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists - History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block - History of Torsade de Point or known history of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome). - Severe cardiovascular diseases diagnosed within 3 months prior to Day 1 of first cycle, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial hypertension. - Any illness or condition that, in the opinion of the Investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient. - Concurrent medical condition that would preclude administration of dexamethasone such as systemic fungal infection or uncontrolled diabetes. Cycles 2 to 4: The following exclusion criteria must be checked prior to inclusion in each repeated cycle: - Lactating woman. - Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient. - Started any of the restricted medications. - Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of reference chemotherapy administration on Day 1. - Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on Day 1 or between Days 1 to 5. - Symptomatic primary or metastatic CNS malignancy. | |
| 46 | NCT02512510 | completed | 1 | phase 3 | ['chronic obstructive pulmonary disease (copd)'] | ["['G91.1', 'I42.1', 'N11.1', 'J05.0', 'P28.42', 'G47.33', 'J44.9']"] | ['td-4208', 'placebo'] | ['CN(CCN1CCC(CC1)OC(=O)NC2=CC=CC=C2C3=CC=CC=C3)C(=O)C4=CC=C(C=C4)CN5CCC(CC5)C(=O)N'] | Inclusion Criteria: - Subject is a male or female subject 40 years of age or older Exclusion Criteria: - Females who are pregnant, lactating, breast-feeding or planning to become pregnant during the study | |
| 47 | NCT02510950 | terminated | low accrual | 0 | phase 1 | ['glioblastoma multiforme', 'astrocytoma, grade iv'] | ["['L51.0', 'L51.8', 'L51.9']"] | ['poly-iclc', 'temozolomide'] | ['CN1C(=O)N2C=NC(=C2N=N1)C(=O)N'] | Inclusion Criteria: - Newly diagnosed histologically confirmed glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. - Patients who had craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted. - Consented to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done under this study or as part of routine care or another research project.) - At least 18 years of age. - Karnofsky performance status ≥ 60% - Normal bone marrow and organ function as defined below: - Absolute neutrophil count ≥ 1,500/mcL - Platelets ≥ 100,000/mcL - Total bilirubin ≤ 1.5 x IULN - AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN - Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal - Systemic corticosteroid therapy is permitted provided dosing is no greater than 4 mg per day (dexamethasone or equivalent) on the day of vaccine administration - Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids - Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. - Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: - As this is a safety and feasibility study, prior immunotherapy will be permitted. However, any prior immunotherapy must be discontinued at least 2 weeks before peptide vaccine administration. Non-immunologic therapy may be continued. - Inadequate tissue acquisition to allow for neoantigen screening - No candidate neoantigen identified during screening - A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy. - Currently receiving any other investigational agents. - Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty. - A history of allergic reactions attributed to compounds of similar chemical or biologic composition to poly-ICLC or other agents used in the study. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - History of pre-existing immunodeficiency disorder including chronic infection (i.e. hepatitis B, hepatitis C, HIV), or autoimmune condition requiring immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. - Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment. - Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of first dose of vaccine. |
| 48 | NCT02514473 | completed | 1 | phase 3 | ['cystic fibrosis'] | ["['E84.9', 'Z14.1', 'E84.0', 'E84.11', 'E84.8', 'E84.19', 'P09.4']"] | ['vx-809', 'placebo', 'vx-770'] | ['CC1=C(N=C(C=C1)NC(=O)C2(CC2)C3=CC4=C(C=C3)OC(O4)(F)F)C5=CC(=CC=C5)C(=O)O', 'CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C'] | Inclusion Criteria: - Subjects who weigh ≥15 kg without shoes a the Screening Visit - Subjects with confirmed diagnosis of CF at the Screening Visit. - Subjects who are homozygous for the F508del CFTR mutation - Subjects with ppFEV1 of ≥70 percentage points adjusted for age, sex, and height - Subjects with a screening LCI2.5 result greater than or equal to 7.5 Exclusion Criteria: - History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject - Clinically significant abnormalities in hemoglobin, liver function, or renal function at the Screening Visit. - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 - History of solid organ or hematological transplantation at the Screening Visit | |
| 49 | NCT02518139 | completed | 1 | phase 3 | ['chronic obstructive pulmonary disease (copd)'] | ["['G91.1', 'I42.1', 'N11.1', 'J05.0', 'P28.42', 'G47.33', 'J44.9']"] | ['td-4208', 'tiotropium'] | ['CN(CCN1CCC(CC1)OC(=O)NC2=CC=CC=C2C3=CC=CC=C3)C(=O)C4=CC=C(C=C4)CN5CCC(CC5)C(=O)N', 'C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C'] | Inclusion Criteria: - Subject is a male or female subject 40 years of age or older Exclusion Criteria: - Females who are pregnant, lactating, breast-feeding or planning to become pregnant during the study | |
| 50 | NCT02518750 | terminated | due to slow accrual | 0 | phase 2 | ['acute lymphoblastic leukemia', "lymphoma, non-hodgkin's", 'leukemia, t-cell', 'leukemia, b-cell'] | ["['C91.01', 'C91.02', 'C91.00']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C91.61', 'C91.62', 'C91.51', 'C91.52', 'C91.60', 'C91.50']", "['C91.31', 'C91.32', 'C91.A1', 'C91.A2', 'C91.11', 'C91.12', 'C91.30']"] | ['dexamethasone', 'panobinostat', 'liposomal vincristine', 'mitoxantrone', 'peg-asparaginase', 'bortezomib', 'intrathecal triples', 'high-dose methotrexate', '6-mercaptopurine', 'high-dose cytarabine', 'nelarabine', 'cyclophosphamide', 'etoposide', 'clofarabine'] | ['CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C', 'CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)C=CC(=O)NO', 'CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O', 'C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO', 'B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O', 'C1=NC2=C(N1)C(=S)N=CN2', 'COC1=NC(=NC2=C1N=CN2C3C(C(C(O3)CO)O)O)N', 'C1CNP(=O)(OC1)N(CCCl)CCCl', 'CC1OCC2C(O1)C(C(C(O2)OC3C4COC(=O)C4C(C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O', 'C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)F)Cl)N'] | Inclusion Criteria: - Participants must have relapsed or refractory acute lymphoblastic leukemia or lymphoma (ALL): - Stratum I: T-cell lymphoblastic leukemia or lymphoma in first relapse or refractory to one or two courses of frontline induction therapy. - Stratum II: B-cell or T-cell lymphoblastic leukemia or lymphoma in second or third relapse or refractory to 2 or 3 induction or re-induction attempts. Patients with Ph+ ALL must be refractory or relapsed after treatment with regimen that included a tyrosine kinase inhibitor (TKI). - Relapse in ALL is defined as the reappearance (in a patient who has previously achieved remission) of leukemic blasts in the bone marrow. - Should flow cytometric analyses suggest relapse (by the reappearance of a similar immunophenotype to the original leukemia) in the presence of <5% blasts morphologically, a repeat bone marrow test is recommended to confirm relapse. - Molecular or genetic relapse is characterized by the reappearance of a cytogenetic or molecular abnormality. - Age is ≤ 21 years (participant has not yet reached 22nd birthday). - Able to swallow capsules. - Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years. - Prior therapy: - There is no waiting period for participants who relapse while receiving therapy if they are free from side effects attributable to such therapy. - Emergent radiation therapy, one dose of intrathecal chemotherapy and up to 7 days of steroids or hydroxyurea are permitted before start of treatment in participants who relapse after completion of frontline therapy. Other circumstances must be cleared by PI or medical designee. - At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for ≥ 2 weeks, if applicable. - Adequate renal function defined as glomerular filtration rate ≥ 60 cc/min/1.73m^2 or serum creatinine based on age as follows: - If age is 1 to 2 years, then maximum serum creatinine (mg/dL) is 0.6 for males or females. - If age is 2 to 6 years, then maximum serum creatinine (mg/dL) is 0.8 for males or females. - If age is 6 to 10 years, then maximum serum creatinine (mg/dL) is 1 for males or females. - If age is 10 to <13 years, then maximum serum creatinine (mg/dL) is 1.2 for males or females. - If age is 13 to 16 years, then maximum serum creatinine (mg/dl) is 1.5 for males or 1.4 for females. - If age is > 16 years, then maximum serum creatinine (mg/dl) is 1.7 for males or 1.4 for females. - Adequate hepatic function defined as: - Direct bilirubin ≤ 1.4 mg/dL (if total bilirubin > 1.4 mg/dL) AND - AST and ALT < 5 x ULN for age. - Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%. - Lymphoma participants without bone marrow involvement must have: - Absolute neutrophil count (ANC) >1,000/mm3, AND - Platelet count ≥50,000/mm^3 (without transfusion support) - NOTE: These criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement. - Written, informed consent and assent following Institutional Review Board, NCI, FDA and OHRP guidelines. Exclusion Criteria: - Prior histone deacytylases (HDAC), DAC, HSP90 inhibitors or valproic acid for treatment of cancer. - Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment. - Impaired cardiac function or clinically significant cardiac diseases, history of arrhythmia (including ventricular fibrillation or torsade de pointes), bradycardia <50 bpm, screening ECG with prolonged QTc or uncontrolled hypertension. - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat. - Patients with diarrhea > CTCAE grade 2. - Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol. - Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting treatment. - Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies. - Patients who have undergone major surgery ≤ 4 weeks prior to starting treatment or who have not recovered from side effects of such therapy. - Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis B/C. - Inability to swallow capsules. - Active, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness. - Isolated extramedullary relapse (leukemia) or isolated CNS lymphoma. - Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment). Male or female of reproductive potential has agreed to use effective contraception method for duration of study treatment. - Down syndrome. - Inability or unwillingness or research participant or legal guardian/representative to give written informed consent. |
| 51 | NCT02511184 | terminated | decision based on the low enrollment mainly due to high efficacy drugs available in 1st line alk-positive nsclc (eg alectinib), not due to any safety concerns | 0 | phase 1 | ['alk-positive advanced nsclc'] | ["['C84.67', 'C84.60', 'C84.62', 'C84.66', 'C84.63', 'C84.68', 'C84.69']"] | ['crizotinib', 'pembrolizumab'] | ['CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N'] | Inclusion Criteria: - Histologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment. - Alk-positive NSCLC as determined by a test that is approved or validated for use as a companion diagnostic test. - No prior systemic therapy for metastatic disease. - Adjuvant chemotherapy more than 12 months prior to study enrollment. - Measurable disease as per RECIST 1.1 - ECOG PS 0 or 1. Exclusion Criteria: - Prior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any drug targeting T-cell checkpoint pathways. - known diagnosis of immunodeficiency or is receiving systemic steroid therapy or other form of immunosuppressive therapy within 7 days of clinical trial treatment. - Active autoimmune disease that has required systemic treatment in the past 3 months. - History of extensive disseminated interstitial fibrosis or any grade of interstitial lung disease. |
| 52 | NCT03688711 | completed | 1 | phase 3 | ['hypoglycemia', 'diabetes mellitus, type 1'] | ["['E16.1', 'E16.2', 'P70.3', 'P70.4', 'E16.0', 'E10.641', 'E10.649']", "['E10.65', 'E10.9', 'E10.21', 'E10.36', 'E10.41', 'E10.42', 'E10.44']"] | ['dasiglucagon', 'placebo'] | ['CC(C)CC(C(=O)NC(CCC(=O)O)C(=O)NC(CO)C(=O)NC(C(C)O)C(=O)O)NC(=O)C(CC1=CNC2=CC=CC=C21)NC(=O)C(CCCCN)NC(=O)C(C(C)C)NC(=O)C(CC3=CC=CC=C3)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(C)NC(=O)C(CCCNC(=N)N)NC(=O)C(C)NC(=O)C(C)(C)NC(=O)C(CC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC5=CC=C(C=C5)O)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC6=CC=CC=C6)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)N)NC(=O)C(CO)NC(=O)C(CC7=CNC=N7)N', 'Status: 503'] | Inclusion Criteria: - Female or male subjects with T1DM for at least 1 year; diagnostic criteria as defined by the American Diabetes Association (3). - Treated with insulin for T1DM for at least 1 year and with stable insulin treatment (defined as no more than a 10-unit daily variation in total daily insulin dose) 30 days prior to screening - Hemoglobin A1c <10%. - Aged between 18 and 75 years, both inclusive. Exclusion Criteria: - Previous participation in a clinical trial within the dasiglucagon in the rescue treatment of hypoglycemia program. - Known or suspected allergy to trial drug(s) or related products. - History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema). - Previous participation in this trial. Participation being defined by signing the informed consent document. | |
| 53 | NCT03687125 | terminated | sponsor decision based on adverse events limiting administration of higher doses required to achieve myeoblative conditioning necessary in this population | 0 | phase 1/phase 2 | ['multiple myeloma in relapse', 'multiple myeloma progression', 'multiple myeloma with failed remission'] | ["['C90.02']"] | ['tinostamustine'] | ['CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCCCCC(=O)NO'] | Inclusion Criteria: 1. Participants has Multiple Myeloma (MM) and: a. Has received prior ASCT after standard first-line induction treatment. b. Has evidence of progressive disease (PD), with progression-free interval greater than or equal to (>=) 6 months in Phase 1 >= 18 months in Phase 2. - Progression Free Interval is defined as the time from date of ASCT to PD. c. Received treatment with lesser than or equal to (<=) 3 prior lines of therapy. - A line of therapy is defined as 1 or more cycles of a planned treatment program. When participants have undergone sequential phases of treatment without intervening progression, such as induction, collection of peripheral blood stem cells (PBSCs), transplantation and consolidation/maintenance, this is considered to be 1 line of treatment. A new line of therapy is initiated as a result of PD or relapse. 2. Complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) to salvage chemotherapy, as determined by the International Myeloma Working Group (IMWG) criteria. 3. Is, in the Investigator's opinion, a candidate for consolidation therapy with tinostamustine followed by ASCT. (Note that participants planned to receive tandem ASCT are not eligible for the Phase 1 portion of the study.) 4. Has available autologous peripheral blood stem cell (PBSC) product with CD34 cell dose >= 2×106 cells/kg. The product could be from a collection prior to first ASCT or later second collection. (Note that, although not required, in Phase 1, the Investigator should consider enrolling participant with a large number of available PBSCs to permit subsequent ASCT, as participants in Stage 1 may received a dose lower than that determined to be effective.) 5. Age 18-75 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status score lesser than (<) 3 at Screening. 7. Creatinine clearance >= 40 milliliter per minute (mL/min), as determined by a local laboratory using the Cockcroft-Gault equation within 28 days before ASCT. 8. Left ventricular ejection fraction (LVEF) >= 40 percent (%) within 28 days before ASCT. 9. Adequate pulmonary function, defined as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) greater than (>) 50% predicted within 28 days before ASCT. 10. Adequate liver function, as defined by an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 × the upper limit of normal (ULN) and bilirubin <= 1.5 × ULN within 28 days before ASCT. 11. Potassium within the local laboratory's normal range. (Potassium supplementation is permissible.) Exclusion Criteria: Participants meeting any of the following criteria are not eligible for study entry: 1. History of central nervous system (CNS) disease involvement. 2. Primary or secondary plasma cell leukemia at any time point prior to transplant. 3. Myocardial infarction (MI) or stroke within 6 months before Screening. 4. Uncontrolled acute infection. 5. Hematopoietic cell transplantation-comorbidity index (HCT-CI) > 6 points. 6. Concurrent malignant disease with the exception of treated basalioma/spinalioma of the skin or early-stage cervix carcinoma, or early-stage prostate cancer. Previous treatment for other malignancies (not listed above) must have been terminated at least 24 months before registration and no evidence of active disease shall be documented since then. 7. Major coagulopathy or bleeding disorder. 8. Other serious medical condition that could potentially interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery. 9. Lack of cooperation to allow study treatment as outlined in this protocol. 10. Pregnancy or lactating female participants. 11. The use of any anti-cancer investigational agents within 21 days prior to the expected start of trial treatment and interval of 14 days to last administration of salvage treatment. 12. Receiving treatment with drugs known to prolong the QT/QTc interval. 13. QTc interval (Fridericia's formula) > 450 millisecond (msec), based on the mean of triplicate Screening 12-lead electrocardiograms (ECGs). |
| 54 | NCT03689894 | terminated | insufficient accrual | 0 | phase 1/phase 2 | ['chronic graft-versus-host-disease'] | ["['D89.811', 'D89.812']"] | ['ibrutinib', 'rituximab'] | ['C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N'] | Inclusion Criteria: 1. Men and women ≥18 years old who are recipients of an allogeneic bone marrow, cord blood or peripheral blood stem cell transplant. (There will be no restrictions based upon underlying disease, donor source, degree of human leukocyte antigen (HLA) match, intensity of pre-transplant conditioning regimen or use of prior donor lymphocyte infusion(s).) 2. Chronic GVHD that is confirmed by clinical assessment and/or biopsy. 3. Either steroid-refractory or steroid-dependent cGVHD. 4. Karnofsky performance status ≥ 60. Exclusion Criteria: 1. History of treatment with a tyrosine kinase inhibitor (eg, imatinib) or other moderate-to-significant Cyclophilin A4 inhibitor within 2 weeks of enrollment. 2. Renal insufficiency as follows: creatinine > 2.5 mg/deciliters (dL) or Creatinine Clearance < 30 ml/min. 3. Hepatic insufficiency as follows: serum bilirubin >3 mg/dL or transaminitis >3x upper limit of normal (ULN) (unless deemed due to GVHD). 4. History of cardiac dysrhythmias or known cardiovascular disease without formal Cardiology clearance. 5. History of cerebro-vascular accident or intracranial hemorrhage within 6 months prior to enrollment. 6. History of non-intracranial hemorrhage and/or coagulopathy without formal Coagulation clearance. 7. Uncontrolled infections not responsive to antibiotics, anti-viral medicines, or anti-fungal medicines; or infection requiring systemic treatment that was completed ≤14 days before enrollment. 8. History of other hematologic malignancy. 9. History of human immunodeficiency virus (HIV). 10. History of active hepatitis B virus (HBV) or hepatitis C virus (HCV) without formal Infectious Disease clearance. 11. Patients incapable of complying with routine follow up schedule or unable to be compliant with study therapy. 12. Active or within 3 months use of prohibited medications or substances (e.g., illicit drugs). |
| 55 | NCT03569033 | terminated | the data did not support study endpoints for acute cough, based on an interim efficacy analysis; not due to safety concerns. | 0 | phase 2 | ['acute cough'] | ["['R05.1']"] | ['gefapixant', 'placebo'] | ['CC(C)C1=CC(=C(C=C1OC2=CN=C(N=C2N)N)S(=O)(=O)N)OC'] | Inclusion Criteria: - In good general health - Susceptible to human rhinovirus type 16 (HRV-16) - Male or non-pregnant and non-breast feeding female - If female of reproductive potential, agrees to use 1 form of acceptable birth control Exclusion Criteria: - Donated blood within 56 days or donated plasma within 7 days prior to dosing - History of significant multiple and/or severe allergies - Recent history of respiratory tract infection - History of cancer - Body mass index <18 kg/m^2 or ≥40 kg/m^2 - History of major surgery or loss of 1 unit of blood - History of allergic reaction to sulfonamides - Received medications within 14 days prior to randomization - Significantly abnormal laboratory tests at Screening - Current smoker, smoked within 5 years of Screening, or significant past smoking history - History of alcohol or drug abuse |
| 56 | NCT03566290 | terminated | lack of efficacy | 0 | phase 2 | ['stress urinary incontinence'] | ["['N39.41', 'N39.46', 'N39.490', 'N39.491', 'N39.492', 'R32', 'R39.81']"] | ['gtx-024'] | ['CC(COC1=CC=C(C=C1)C#N)(C(=O)NC2=CC(=C(C=C2)C#N)C(F)(F)F)O'] | Inclusion Criteria: - Be an eligible subject from G201002, where an eligible subject is defined as: 1. one of the first 225 subjects who were randomly assigned to the placebo group in G201002 and who have completed the required treatment and durability periods of that study, or; 2. any subject from 226 onwards, who was randomly assigned to any treatment group and who completed the required treatment and follow-up periods of that study - Be able to read, understand, and provide written, dated, informed consent prior to enrollment in the current study and be likely to comply with the study protocol and communicate with study personnel about AEs and other clinically important information - Provide written consent to participate in the study within the following timeframes: 1. for G201002 Subjects 1-225, within 30 days after unblinding of G201002 (subjects who consent to participate in G201003 will be allowed to discontinue from that study and consent to this study upon unblinding of G201002) 2. for G201002 Subjects 226-493, within 30 days of completing both the treatment and follow-up periods of G201002 - Agree to maintain a stable dose of any medication known to affect lower urinary tract function, including but not limited to anticholinergics, tricyclic antidepressants, beta-3 adrenergic agonists, or α-adrenergic blockers, throughout the duration of the study Exclusion Criteria: - Starts any new treatment (medication, pelvic floor physical therapy, or other treatment known to impact the pelvic floor) after completing G201002 that is known or suspected to affect lower urinary tract function, including vaginal rejuvenation - Subject is currently taking systemic sex-hormone products (excludes intravaginal application of estradiol topical/tablet agents and hormones delivered via vaginal rings) - Has a current cancer diagnosis (with the exception of nonmelanoma skin cancer) or any history of breast or endometrial cancer - Has a known history or current episode of: 1. New York Heart Association Stage ≥ 2 hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg) at screening and/or baseline. Subjects with hypertension that has been treated and controlled with medication for ≥ 2 weeks prior to screening are eligible for participation 2. Recent myocardial infarction or arterial or venous thromboembolic event (within 1 year) or a history of more than 1 myocardial infarction or arterial or venous thromboembolic event 3. Cardiac-related syncopal event within the past year 4. Cardio or cerebral vascular disease requiring surgical intervention (e.g., bypass surgery, angioplasty). For subjects with previous stent placement, please contact the medical monitor 5. Congestive heart failure of Stage > 2 according to New York Heart Association criteria 6. Angina pectoris - Has a current or past history of any physical condition that, in the investigator's opinion, might put the subject at risk, impact the absorption of the study drug, or interfere with interpretation of study |
| 57 | NCT03566485 | terminated | low accrual/loss of funding | 0 | phase 1/phase 2 | ['stage iii breast cancer', 'stage iiia breast cancer', 'stage iiib breast cancer', 'stage iiic breast cancer', 'stage iv breast cancer', 'estrogen receptor-positive', 'her2/neu negative'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['Z17.0']", "['A41.50', 'A41.59', 'E70.320', 'Z17.1', 'Z67.11', 'Z67.21', 'Z67.31']"] | ['atezolizumab', 'cobimetinib', 'idasanutlin'] | ['C1CCNC(C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O', 'CC(C)(C)CC1C(C(C(N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F'] | - Signed and dated written informed consent. - Subjects ≥ 18 years of age. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. - Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is: - ER/PR-positive (> 1% cells) by IHC and HER2 negative per ASCO guidelines (by IHC or FISH) - Previously exposed to an aromatase inhibitor (AI) or a selective estrogen-receptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor - Appropriate candidates for chemotherapy - Amenable to biopsy at the time of study entry - Adequate organ function including: - Absolute neutrophil count (ANC) ≥ 1.5 × 109/L - Platelets ≥ 100 × 109/L - Hemoglobin ≥ 9/g/dL (may have been transfused) - Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN) - Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present) - Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault (CG) equation - Thyroid Stimulating Hormone (TSH) ≤ 1 x ULN - Amylase ≤ 1 x ULN - Lipase ≤ 1 x ULN - CPK ≤ 1.5 x ULN - LVEF (echo) ≥ LLN (Cobi arm only) - Female patients of childbearing potential must agree to use at least two methods of acceptable contraception with a failure rate of < 1% per year from 15 days prior to first trial treatment administration until at least 5 months after study participant's final dose of study drugs. See appendix C for details. Note: Females of childbearing potential are defined as those who are not surgically sterile or post-menopausal (i.e. patient has not had a bilateral tubal ligation, a bilateral oophorectomy, or a complete hysterectomy; or has not been amenorrheic for 12 months without an alternative medical cause). Post-menopausal status in females under 55 years of age should be confirmed with a serum follicle-stimulating hormone (FSH) level within laboratory reference range for postmenopausal women. - Patients unable to read/write in English are eligible to participate in the overall study but will not participate in the Patient-Reported Outcome questionnaires throughout the trial - Re-enrollment of a subject that has discontinued the study as a pre-treatment screen failure (i.e. a consented patient who did not receive study drugs) is permitted. If re-enrolled, the subject must be re-consented. Only the screening procedures performed outside of protocol-specified timing must be repeated. Exclusion Criteria: - Prior therapy with anti-PD-L1 and anti-PD1 antibodies, MEK inhibitors or MDM2 antagonists. - No more than 3 lines of chemotherapy in the metastatic setting - No concurrent anticancer therapy. Required washout from prior therapy: - Endocrine therapy: no required wash-out - Chemotherapy: 14 days - Major surgery: 14 days (provided wound healing is adequate) - Radiation: 7 days - Investigational/Biologic Therapy (half -life ≤ 40 hours): 14 days - Investigational/Biologic Therapy (half -life > 40 hours): 28 days - Use of corticosteroids or immunosuppressive medication is exclusionary, except the following in the absence of active autoimmune disease: - Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhaled); - Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent are permitted; - Adrenal replacement steroid doses including doses > 10 mg daily prednisone are permitted; - A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT scan premedication against contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted. - Previous malignant disease other than breast cancer within the last 5 years, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment). - All subjects with brain metastases, except those meeting the following criteria: - Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment - No history of intracranial or spinal cord hemorrhage - No evidence of interim CNS disease progression - Metastasis to the midbrain, pons, and medulla - No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable. - Subjects must be either off steroids or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) - Receipt of any organ transplantation including allogeneic stem-cell transplantation. - Significant acute or chronic infections including, among others: - Known history of testing positive for human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS). - Active tuberculosis - Positive test for hepatitis B virus (HBV) surface antigen (and/or core antibody) and/or confirmatory hepatitis C virus (HCV) RNA (if anti-HCV antibody tested positive). - Active autoimmune disease with reasonable possibility of clinically significant deterioration when receiving an immunostimulatory agent: - Subjects with Type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. - Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day. - Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable. - Interstitial lung disease that is symptomatic or which may interfere with the detection or management of suspected drug-related pulmonary toxicity. - Uncontrolled asthma [defined as having 3 or more of the following features of partially controlled asthma within 28 days prior to starting study treatment: Daytime symptoms more than twice per week, any limitation of activities, any nocturnal symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known lung function (PEF or FEV1) without administration of a bronchodilator that is < 80% predicted or personal best (if known)]. - Current symptomatic congestive heart failure (New York Heart Association > class II), unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable angina (e.g. new, worsening or persistent chest discomfort), or uncontrolled hypertension (systolic > 160 mmHg or diastolic > 100mmHg). Or any of the following occurring within 6 months (180 days) prior to first dose of study drugs: Myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack. (Use of antihypertensive medication to control blood pressure is allowed.) - Concurrent treatment with a non-permitted drug (refer to prohibited medication list) as well as foods or supplements that are strong or moderate CYP3A4 enzyme inducers or inhibitors. Any of the above has to be discontinued at least 7 days prior to Cycle 1/ Day 1 of study treatment. - Requirement of anticoagulant therapy with oral vitamin K antagonists such as Coumadin (warfarin). Low-dose anticoagulants for the maintenance of patency in a central venous access device or the prevention of deep vein thrombosis or pulmonary embolism is allowed. Therapeutic use of low molecular weight heparin is allowed provided patients are safely able to interrupt it prior to biopsy procedures. - Persisting toxicity related to prior therapy that has not reduced to Grade 1 [National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0]; however, alopecia and sensory neuropathy Grade ≤ 2 are acceptable and Grade ≤ 2 non-hematological toxicities well controlled with medical management are allowed (for example: hypomagnesemia well controlled on magnesium replacement). - Known severe (Grade ≥ 3 NCI-CTCAE) hypersensitivity reactions to monoclonal antibodies, or history of anaphylaxis. - Vaccination within 28 days of the first dose of study drugs and while on trial is prohibited, except for administration of inactivated vaccines (for example, inactivated influenza vaccine). - Pregnant or breastfeeding females. - Known current alcohol or drug abuse - Prisoners or subjects who are involuntarily incarcerated. - Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the patient's study physician to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with scheduled visits, treatment schedule, laboratory tests and other study requirements. - Known risk factors for ocular toxicity, consisting of any of the following (Cobi arm only): - presence of serous retinopathy within 6 months of protocol enrollment - presence of retinal vein occlusion (RVO) within 6 months of protocol enrollment |
| 58 | NCT03525444 | completed | 1 | phase 3 | ['cystic fibrosis'] | ["['E84.9', 'Z14.1', 'E84.0', 'E84.11', 'E84.8', 'E84.19', 'P09.4']"] | ['vx-445/tez/iva', 'iva', 'placebo'] | ['Status: 400', 'CC(C)CC(=O)O'] | Key Inclusion Criteria: - Heterozygous for the F508del mutation (F/MF) - Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: - Clinically significant cirrhosis with or without portal hypertension - Lung infection with organisms associated with a more rapid decline in pulmonary status - Solid organ or hematological transplantation Other protocol defined Inclusion/Exclusion criteria may apply | |
| 59 | NCT03520985 | terminated | feasibility (low patient accrual and financial reasons) | 0 | phase 2 | ['refractory multiple myeloma'] | ["['D46.4', 'I20.2', 'D46.1', 'D46.A', 'D46.0', 'D46.20', 'D46.21']"] | ['pomalidomide', 'dexamethasone'] | ['C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N', 'CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C'] | Key inclusion criteria: - Patient was diagnosed with multiple myeloma based on standard IMWG criteria - Prior treatment with ≥ 2 treatment lines of anti-myeloma therapy - Patients must have been exposed to both lenalidomide and bortezomib - Measurable disease for myeloma defined as one of the following: serum M-protein ≥ 5 g/L; urine M-protein ≥ 0.2 g/24 hours - Refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy. - Adequate hematological and hepatic function - A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential Key exclusion criteria: - History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration, with the exception of pT1-2 prostate cancer Gleason score ≤6, adequately treated, cervical carcinoma in situ or localized non-melanoma skin cancer. - Polyneuropathy grade > 2 - Patients who received any of the following within the last 14 days of initiation of trial treatment: - Plasmapheresis - Major surgery (kyphoplasty is not considered major surgery) - Radiation therapy - Use of any anti-myeloma drug therapy - Known or clinically suspected myeloma manifestations in the central nervous system - Severe or uncontrolled cardiovascular disease |
| 60 | NCT03525548 | completed | 1 | phase 3 | ['cystic fibrosis'] | ["['E84.9', 'Z14.1', 'E84.0', 'E84.11', 'E84.8', 'E84.19', 'P09.4']"] | ['vx-445/tez/iva', 'tez/iva', 'iva', 'placebo', 'placebo'] | ['Status: 400', 'Status: 400', 'CC(C)CC(=O)O'] | Key Inclusion Criteria: - Homozygous for the F508del mutation (F/F) - Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: - Clinically significant cirrhosis with or without portal hypertension - Lung infection with organisms associated with a more rapid decline in pulmonary status - Solid organ or hematological transplantation Other protocol defined Inclusion/Exclusion criteria may apply | |
| 61 | NCT04190056 | terminated | low accrual | 0 | phase 2 | ['anatomic stage iv breast cancer ajcc v8', 'prognostic stage iv breast cancer ajcc v8'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['tamoxifen', 'vorinostat'] | ['CCC(=C(C1=CC=CC=C1)C2=CC=C(C=C2)OCCN(C)C)C3=CC=CC=C3', 'C1=CC=C(C=C1)NC(=O)CCCCCCC(=O)NO'] | Inclusion Criteria: - Pre and postmenopausal women or men with stage IV ER+ breast cancer histological or cytological confirmation - > 10% expression of PD-1/Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) dual staining in Cluster of differentiation 8 (CD8) cells in tumor or blood or >5% expression of PD-1/CTLA-4 dual staining in CD4 in blood (only). - Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 - Understand and voluntarily sign an informed consent prior to any study-related assessments or procedures are conducted and are able to adhere to the study visit schedule and other protocol requirements - Consent to paired tumor biopsy - Measurable tumor by Response Evaluation Criteria in Solid Tumors (RECIST) criteria - Per Good Clinical Practice, any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with anti-PD1 therapy should be resolved to less than grade 1 - Absolute neutrophil count (ANC) >= 1.5 X 10^9/L - Hemoglobin (Hgb) >= 9 g/dL (may transfuse if clinically indicated) - Platelets (plt) >= 100 x 10^9/L - Potassium within normal range, or correctable with supplements - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit normal (ULN) or =< 5.0 x ULN if liver tumor is present - Serum total bilirubin =< 1.5 x ULN - Serum creatinine =< 1.5 x ULN, or 24-hr clearance >= 60 ml/min - Females of childbearing potential (defined as sexually mature women who): - Has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, - Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months) must have - Negative serum pregnancy test within 14 days before starting study treatment in females of childbearing potential (FCBP) and willingness to adhere to acceptable forms or birth control (a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) - All female and male participants must agree to use approved contraception during the treatment period and for at least 18 weeks after the last dose of study treatment and refrain from donating sperm during this period Exclusion Criteria: - Prior treatment with pembrolizumab or other PD-(L)1 - Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study - Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/ interstitial lung disease - Has known active hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) [qualitative] is detected) - Has a history of hepatitis B virus (HBV) - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator - Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed - Persistent diarrhea or malabsorption >= National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2, despite medical management - Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure - Prior systemic cancer-directed treatments or investigational modalities =< 5 half-lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy (except alopecia) - Active autoimmune disease except for vitiligo or hypothyroidism - Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis) - Major surgery =< 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy - Pregnant or breastfeeding - Known human immunodeficiency virus (HIV) infection - Known history of tuberculosis - Known allergic reaction or intolerability to tamoxifen - Patients with prior history of deep vein thrombosis (DVT)s must be on therapeutic or preventive anticoagulation |
| 62 | NCT04190433 | withdrawn | administratively closed due to low/no accrual | 0 | phase 2 | ['breast carcinoma', 'hematopoietic and lymphoid cell neoplasm', 'lymphoma', 'sarcoma'] | ["['C4A.52', 'C44.511', 'C44.521', 'D05.00', 'D05.01', 'D05.02', 'D05.10']", "['C96.20', 'C96.29', 'D47.09']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C96.A', 'C46.9', 'C96.22', 'C46.0', 'C46.2', 'C92.31', 'C92.32']"] | ['carvedilol', 'lisinopril', 'pravastatin', 'spironolactone'] | ['COC1=CC=CC=C1OCCNCC(COC2=CC=CC3=C2C4=CC=CC=C4N3)O', 'C1CC(N(C1)C(=O)C(CCCCN)NC(CCC2=CC=CC=C2)C(=O)O)C(=O)O', 'CCC(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC(CC(CC(=O)O)O)O)O', 'CC(=O)SC1CC2=CC(=O)CCC2(C3C1C4CCC5(C4(CC3)C)CCC(=O)O5)C'] | Inclusion Criteria: - >= 18 years of age. - New diagnosis of reduced cardiac function. - Any prior anthracycline-based cancer therapy for hematological malignancy, breast cancer, or sarcoma. Exclusion Criteria: - History of heart failure (HF) of any class and type, or diagnosis of cardiomyopathy prior to anthracycline therapy. - On active therapy with a fibrate, niacin or eplerenone, or statin. - History of myopathy/rhabdomyolysis. - History of statin intolerance. - Active treatment for hyperlipidemia. - History of gout. - Active treatment for liver disease. - Unexplained persistent elevations of serum transaminases (above upper limit of normal over two weeks). - Pregnancy. - Breast-feeding. - Hyperkalemia (above upper limit of normal). - Addison disease. - Estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m^2. |
| 63 | NCT03433677 | completed | 1 | phase 3 | ['diabetes type 1'] | ["['E10.65', 'E10.9', 'E10.21', 'E10.36', 'E10.41', 'E10.42', 'E10.44']"] | ['ly900014', 'insulin lispro'] | ['CCC(C)C(C(=O)NC(C(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)N)C(=O)NC(CS)C(=O)NC(CS)C(=O)NC(C(C)O)C(=O)NC(CO)C(=O)NC(C(C)CC)C(=O)NC(CS)C(=O)NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC1=CC=C(C=C1)O)C(=O)NC(CCC(=O)N)C(=O)NC(CC(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(CC(=O)N)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CS)C(=O)NC(CC(=O)N)C(=O)O)NC(=O)CN.CC(C)CC(C(=O)NC(CC1=CC=C(C=C1)O)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CS)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC2=CC=CC=C2)C(=O)NC(CC3=CC=CC=C3)C(=O)NC(CC4=CC=C(C=C4)O)C(=O)NC(C(C)O)C(=O)NC(CCCCN)C(=O)N5CCCC5C(=O)NC(C(C)O)C(=O)O)NC(=O)C(C)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC6=CN=CN6)NC(=O)C(CO)NC(=O)CNC(=O)C(CS)NC(=O)C(CC(C)C)NC(=O)C(CC7=CN=CN7)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC8=CC=CC=C8)N'] | Inclusion Criteria: - Diagnosed with type 1 diabetes and have been using insulin continuously for at least 12 months. - Using an insulin pump with 'rapid-acting insulin' for at least 6 months and using the same rapid-acting insulin for at least the past 30 days. - Have experience using Continuous Glucose Monitoring (CGM) or Flash Glucose Monitoring (FGM) for at least 60 days during the past 12 months. - Have hemoglobin A1c values ≤8.5%, as determined by the central laboratory at screening. - Have a body mass index (BMI) of ≤35 kilograms per meter squared at screening. - Have been using the MiniMed 530G or 630G (US) or the MiniMed 640G (EU) insulin pump for at least the past 30 days. Exclusion Criteria: - Have had more than 1 emergency treatment for very low blood glucose in the last 6 months. - Have had more than 1 emergency treatment for poor glucose control (hyperglycemia or diabetic ketoacidosis) in the last 6 months. - Have significant insulin resistance defined as having received a total daily dose of insulin >1.2 units per kilogram (U/kg) at screening, as determined by the average total daily insulin dose over the 3 days prior to screening divided by weight in kilograms based on investigator review of the participant's pump history. - Have significant lipohypertrophy, lipoatrophy, or scars within the subcutaneous tissue in areas of infusion or have a history of abscess at an infusion site within the last 90 days prior to screening. - Are receiving any oral or injectable medication intended for the treatment of diabetes mellitus other than rapid-acting analog insulin via CSII in the 90 days prior to screening. Occasional pen or syringe injection of insulin is allowed, for example, due to pump malfunction or unexplained hyperglycemia not responsive to pump correction bolus. - Taking certain diabetes medications that are not allowed for study participation. - Have major problems with heart, kidneys, liver, or have a blood disorder. - Have had or are now being treated for certain types of cancer that prevents study participation. | |
| 64 | NCT03436420 | terminated | terminated due to lack of efficacy and safety concerns. | 0 | phase 2 | ['non-alcoholic fatty liver disease'] | ["['Z52.6', 'K71.8', 'K71.7', 'A06.4', 'C22.0', 'C22.3', 'K70.0']"] | ['gemcabene'] | ['CC(C)(CCCCOCCCCC(C)(C)C(=O)O)C(=O)O'] | Inclusion Criteria: 1. Provision of signed and dated informed consent form 2. Provision of signed and dated assent, if indicated 3. Stated willingness to comply with all study procedures and availability for the duration of the study 4. Children aged 12-17 years at the time of informed consent 5. History of clinical diagnosis of NAFLD including a, b and c below: 1. Medical history eliminating, other chronic liver diseases (for example mitochondrial diseases, hepatotoxic drugs, anorexia nervosa) 2. Laboratory studies: negative testing for hepatitis C and normal ceruloplasmin 3. Either liver biopsy confirming NAFLD or MRI > 10% steatosis within the past three years 6. ALT ≥ 54 U/L for boys or ≥ 46 U/L for girls and ≤ 250 U/L at screening visit and within past three months (prior to screening). If ALT at screening is more than two times the historic value (or a historic value is not available), the subject will be asked to repeat the ALT after four weeks. If the repeat ALT is more than 50% increased or decreased over the screening ALT a third ALT may be obtained. If a third ALT is not within 50% of the previous value then the subject is ineligible, but may be rescreened at a later date. 7. Body weight ≥ 60 kg at the time of screening 8. Able to take oral medication and be willing to adhere to the study drug regimen 9. Minimum of three months of attempted lifestyle modification to treat the NAFLD and agreement to adhere to Lifestyle Considerations (dietary improvement and physical activity) throughout study duration Exclusion Criteria: 1. Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias) 2. Seizure disorder 3. Active coagulopathy (international normalized ratio (INR) > 1.4) 4. Renal dysfunction with an estimated glomerular filtration rate (eGFR) <60ml/min/1.73 calculated using Schwartz Bedside GFR calculator for children 5. History of active malignant disease requiring chemotherapy or radiation 6. History of significant alcohol intake (AUDIT questionnaire) or inability to quantify alcohol consumption 7. Use of new medications or supplements with the intent to treat NAFLD/nonalcoholic steatohepatitis (NASH) during the 30 days prior to screening, including statin therapy. Medications or supplements (including metformin and vitamin E) that they have been on and are on a stable dose are acceptable 8. History of bariatric surgery or planning to undergo bariatric surgery during study duration 9. Clinically significant depression 10. Any girl nursing, planning a pregnancy, known or suspected to be pregnant, or who has a positive pregnancy screen 11. Non-compensated liver disease defined as cirrhosis and any one of the following hematologic, biochemical, and serological criteria on entry into protocol: - Hemoglobin < 10 g/dL; - White blood cell (WBC) < 3,500 cells/mm3; - Neutrophil count < 1,500 cells/mm3; - Platelets < 150,000 cells/mm3; - Total bilirubin > 1.3 mg/dL unless due to Gilbert's syndrome (subjects with a history of Gilbert's syndrome may be included if both direct bilirubin and the reticulocyte count do no exceed the upper limit of normal (ULN) [reflexive direct bilirubin testing will be used to confirm Gilbert's syndrome]) - Albumin < 3.2 g/dL - INR > 1.3 - Abnormal alkaline phosphatase - Any history of ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma (HCC) 12. Poorly controlled diabetes mellitus (hemoglobin A1c (HbA1c) > 8%) or requiring insulin 13. Patients with type I diabetes mellitus 14. Chronic liver disease other than NAFLD 15. Patients on Cytochrome P450 3A4 (CYP3A4) inhibitors such as itraconazole or macrolide antibiotics are excluded 16. Patients who are on thiazolidinediones, fibrates or fish oils are excluded 17. Patients who are on daily prescription medications are excluded except for allergy medications, Attention Deficit Hyperactivity Disorder (ADHD) medications, asthma medications, or any other acceptable medication in the opinion of the investigator 18. Abnormal creatinine kinase levels at screening (may be repeated if the elevation is thought to be exercise related) 19. Sexually active female participants of childbearing potential and Tanner stage ≥ 4 or menstruating unwilling to utilize two acceptable forms of contraception from screening through completion of the study or unwilling to complete pregnancy tests throughout the study 20. Currently enrolled in a clinical trial or who received an investigational study drug within 90 days of screening 21. Participants who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator |
| 65 | NCT04634110 | terminated | low accrual | 0 | phase 2 | ['brain metastases', 'lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['brigatinib'] | ['CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC'] | Inclusion Criteria: 1. Provision to sign and date the consent form. 2. Stated willingness to comply with all study procedures and be available for the duration of the study. 3. Ability to take and retain oral medications. 4. Age ≥18 years. 5. Patients with ALK+ lung cancer with evidence of ≥1 previously untreated brain metastases on brain MRI. Prior therapy (radiation or surgery) for brain metastases is allowed. However, patients must have ≥1 previously untreated at the time of enrollment. 6. Patients may be ALK TKI naïve OR have had prior crizotinib therapy. 7. Patients may be included if they are asymptomatic from their brain metastases (RTOG/EORTC grade 0) or if they have mild symptoms from their brain metastases not to exceed RTOG/ EORTC grade 1 or 2 (Grade 1: Fully functional status (i.e. able to work) with minor neurological findings, no medication needed; Grade 2: Neurological findings present sufficient to require home care / nursing assistance may be required / medications including steroids/anti-seizure agents may be required) (Cox, James D., et al "Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC)." International Journal of Radiation Oncology• Biology• Physics 31.5 (1995): 1341-1346). 8. Neurologically symptomatic patients must not require immediate surgical or radiation therapy for their symptoms, as decided by an investigator. 9. Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2. 10. Have adequate organ function, as determined by - ALT/AST ≤2.5 × upper limit of normal (ULN); ≤5 × ULN is acceptable if liver metastases are present - Total serum bilirubin ≤1.5 × ULN (<3.0×ULN for patients with Gilbert syndrome) - Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, using the modification of diet in renal disease (MDRD) equation - Serum lipase/amylase ≤1.5 × ULN - Absolute neutrophil count (ANC) ≥1.5 × 109/L - Platelet count ≥75 × 109/L - Hemoglobin ≥9 g/dL 11. For females of childbearing potential, have a negative pregnancy test documented prior to initiating brigatinib. 12. For female and male patients who are fertile, agree to use 2 effective methods of contraception with their sexual partners from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Brigatinib may decrease effectiveness of hormonal contraceptives, therefore, women are recommended to use non-hormonal methods of contraception. Highly effective non-hormonal birth control for women of child bearing potential with male partners includes: - Sexual abstinence (no sexual intercourse) - Intrauterine device (IUD) or intrauterine system (IUS) - Bilateral tubal ligation (both tubes tied) - Vasectomized partner 13. Male patients, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following: - Practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from heterosexual intercourse. Exclusion Criteria: 1. Patients who have received prior brigatinib therapy or other CNS-penetrant ALK TKIs, including alectinib, lorlatinib, or ceritinib. 2. RTOG/EORTC Acute CNS symptoms, grade 3 and 4 (Grade 3: Neurological findings requiring hospitalization for initial management; Grade 4: Serious neurological impairment that includes paralysis, coma, or seizures > 3 per week despite medication / hospitalization required). 3. Currently pregnant, planning a pregnancy during the study period, or breastfeeding. 4. Have clinically significant, uncontrolled cardiovascular disease per investigator, specifically including, but not restricted to: 1. Myocardial infarction (MI) within 6 months prior to the first dose of study drug 2. Unstable angina within 6 months prior to first dose of study drug 3. Clinically significant congestive heart failure (CHF) within 6 months prior to first dose of study drug 4. History of clinically significant atrial or ventricular arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician 5. Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug 5. Have uncontrolled hypertension per the investigator. Patients with persistent hypertension of systolic ≥140 or diastolic ≥90 mm Hg should be under treatment on study entry to control blood pressure. 6. Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis. 7. Have an ongoing or active infection, including, but not limited to, the requirement for intravenous (IV) antibiotics. 8. Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history. 9. Have a known or suspected hypersensitivity to brigatinib or its excipients. 10. Additional systemic therapies for the treatment of lung cancer may not be taken concomitantly with brigatinib (eg, TKIs, immunotherapy, chemotherapy). No washout period is required for prior therapy. 11. Have malabsorption syndrome or other GI illness that could affect oral absorption of brigatinib. 12. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of brigatinib. 13. Received systemic treatment with strong cytochrome p-450 (cyp)3a inhibitors, strong cyp3a inducers, or moderate cyp3a inducers within 14 days before enrollment. 14. Had major surgery within 30 days of the first dose of brigatinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed. 15. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy. |
| 66 | NCT04630730 | suspended | temporarily suspended for accrual due to "out of specification" notification for imp batch. | 0 | phase 2 | ['bladder cancer'] | ["['D30.3', 'C67.5', 'C67.9', 'C79.11', 'C67.0', 'C67.1', 'D41.4']"] | ['recombinant intravesical bcg (bacillus calmette-guérin vpm1002bc)', 'atezolizumab', 'cisplatin', 'gemcitabine'] | ['N.N.Cl[Pt]Cl', 'C1=CN(C(=O)N=C1N)C2C(C(C(O2)CO)O)(F)F'] | Inclusion Criteria: - Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures - Histologically proven urothelial cell carcinoma of the bladder (cT2, cT3 or cT4a and ≤ cN1 (defined as a solitary lymph node ≤ 2 cm in the greatest dimension) and cM0) and be considered suitable for curative multimodality treatment including radical cystectomy by a multidisciplinary tumor board - All histological subtypes eligible with the exception of small cell component - Age ≥ 18 years - WHO performance status 0-1 - Hematological function: hemoglobin ≥ 90 g/L, neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L - Hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST ≤ 2.5 x ULN and ALT ≤ 2.5 x ULN, AP ≤ 2.5 x ULN - Renal function: estimated glomerular filtration rate (eGFR) > 50 mL/min/1.73m², according to CKD-EPI formula - Women of childbearing potential must use effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and until 5 months after the last dose of investigational drug - Men agree not to donate sperm or to father a child during trial treatment and until 5 months after the last dose of investigational drug (www.swissmedicinfo.ch). Exclusion Criteria: - Any pathological evidence of small-cell carcinoma component - Presence of any distant metastasis - History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years after registration, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer or low risk localized prostate cancer (T1-T2a, Gleason <7, PSA <10ng/ml) - Residual urinary bladder volume after micturition > 150ml (measured by ultrasound of bladder or inserted catheter) - Prior treatment for bladder cancer including BCG instillations. Single dose intravesical chemotherapy instillation after TURB is allowed - Bladder surgery or traumatic catheterization or TURB within 14 days prior to the expected start of BCG trial treatment - Uncontrollable urinary tract infection, macroscopic haematuria, suspicion of bladder perforation, urethral strictures (if interfering with trial procedures) - Any conditions preventing the patient from keeping BCG instillation in the bladder for at least 1 hour; anticholinergics are allowed to achieve this criterion - Any previous treatment with a PD-1 or PD-L1 inhibitor, including atezolizumab - Concomitant or prior use of immunosuppressive medication within 28 days before registration, with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids which must not exceed 10 mg/day of prednisone (or a dose equivalent corticosteroid) and the premedication for chemotherapy - Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 28 days prior to registration - Major surgical procedure within 28 days prior to registration - Preexisting peripheral neuropathy (> grade 1) - Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients without active disease in the last 5 years may be included but only after consultation with the coordinating investigator - Patients with celiac disease controlled by diet alone - Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment - Known history of tuberculosis, known history of primary immunodeficiency, known history of allogeneic organ transplant, or receipt of live attenuated vaccine within 28 days prior to registration - Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled hypertension - Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information - Known hypersensitivity to trial drugs or to any component of the trial drugs - Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications. |
| 67 | NCT04639245 | terminated | terminated due to slow accrual. | 0 | phase 1/phase 2 | ['anatomic stage iv breast cancer ajcc v8', 'metastatic lung non-small cell carcinoma', 'metastatic malignant solid neoplasm', 'metastatic triple-negative breast carcinoma', 'metastatic urothelial carcinoma', 'stage iv lung cancer ajcc v8'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['D02.20', 'D02.21', 'D02.22']", "['R18.0', 'C17.3', 'G21.0', 'J91.0', 'C05.2', 'C10.0', 'C16.0']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['atezolizumab', 'cyclophosphamide', 'fludarabine'] | ['C1CNP(=O)(OC1)N(CCCl)CCCl', 'C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)O)F)N'] | Inclusion Criteria: - Tissue confirmation of triple negative breast cancer (TNBC), urothelial carcinoma or non-small cell lung cancer (NSCLC) and expression of MAGEA1: Participants must have metastatic disease. Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)/University of Washington Medical Center (UWMC). Patients with TNBC must meet the American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) definition of negative estrogen, progesterone and HER2 receptor expression. Baseline tissue will be stained to confirm MAGE-A1 expression - Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as >= 10 mm, unless lymph node in which case short axis must be >= 15 mm. Baseline imaging (for example diagnostic computed tomography [CT] chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain imaging (magnetic resonance imaging [MRI] or CT scan) must be obtained within 45 days of prior to start of first planned FH-MAGEA1-A2TCR infusion. MRI can be substituted for CT in patients unable to have CT contrast. Measurable disease is not required for purposes of leukapheresis /cell manufacturing storage for patients who meet HLA and expression criteria but not standard treatment criteria - Previous treatment with standard of care (SOC) Food and Drug Administration (FDA)-approved therapies. Patients with NSCLC who have actionable somatic mutations or alterations in EGFR, ROS1 and ALK with FDA-approved drug therapy options will be eligible for study only after treatment with targeted therapies for those mutations have been offered or received. Patients with urothelial carcinoma who are candidates for enfortumab vedotin (enfortumab vedotin-ejfv) will be eligible for study after prior treatment with enfortumab vedotin-ejfv has been offered or received * Note: Participants will be eligible to enroll before standard therapy is received in order to expedite leukapheresis/cell manufacturing as long as the aforementioned agent is administered prior to lymphodepletion and/or cell infusion - Previous treatment with PD-1 axis inhibitor: Patients in Phase I/2 must have been offered or been previously treated with at least one dose of a PD-L1 axis inhibitor (e.g. PD-1 or PD-L1 inhibiting monoclonal antibody such as pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab). If received, they must have either developed progression or still have detectable disease and not have developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicity while on treatment. Patients may have received 1 or more prior systemic regimens for metastatic TNBC or NSCLC. There is no upper limit on prior regimens. Patients may have received prior anti-PD-1/anti-PD-L1 in the neoadjuvant or adjuvant setting - HLA type HLA-A*02:01: Participants must be HLA-A*02:01 in order for infused transgenic T cells in order to insure recognition of antigen-MHC complexes. HLA typing should be determined though a molecular approach in a clinical laboratory licensed for HLA typing - Life expectancy must be anticipated to be > 3 months at trial entry - 18 years or older - Capable of understanding and providing a written informed consent - If fertile, willingness to comply with reproductive requirements - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Tumor tissue amenable to safe biopsy and subject willing to undergo serial tumor biopsies: Should there be no tumor tissue that is accessible for biopsy, patients will still be considered for participation, at discretion of the sponsor and in consultation with the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons biopsies may be cancelled or retimed after confirming plan with the sponsor - Participants must be at least three weeks from last systemic treatment at the time of cell collection: At least 3 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), small molecule or chemotherapy cancer treatment, other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates are permitted but the concurrent treatment with RANK ligand inhibitors (i.e., denosumab) is not permitted within 8 weeks of treatment - Serum creatine < 2.5 mg/dL or estimated glomerular filtration rate (eGFR) > 30 mL/min - Total bilirubin (tBili) < 3.0 mg/dL. Patients with suspected Gilbert syndrome may be included if Tbili > 3 but no other evidence of hepatic dysfunction - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN) - =< grade 1 dyspnea and oxygen saturation (SaO2) >= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) >= 50% of predicted and carbon monoxide diffusing capability test (DLCO) (corrected) of >= 40% of predicted will be eligible - Patients 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or multigated acquisition scan (MUGA) scan, and left ejection fraction must be >= 35%. Cardiac evaluation for other patients is at the discretion of the treating physician - Absolute neutrophil count (ANC) > 500 cells/ mm^3 Exclusion Criteria: - Expression of HLA B*4901: participants will be excluded due to the risk of alloreactivity - Participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment. Childbearing potential is defined as women who have not been surgically sterilized and who are not postmenopausal (free of menses for at least 1 year) - Patients with active autoimmune disease requiring immunosuppressive therapy are excluded. Case-by-case exemptions are possible with approval by principal investigator (PI) - Prior solid organ transplant or allogenic hematopoietic stem cell transplant: Kidney transplant patients will be considered on a case-by-case basis requiring discussion with PI. If kidney transplant, patient must have dialysis access, dialysis plan, supportive nephrologist, willingness to stop transplant immunosuppression, and express understanding that rejection is possible outcome. Dialysis or costs related to transplant kidney will not be supported by the study. Participants having had any other solid organ transplants will be excluded, as will those with any history of allogeneic stem cell transplant - Corticosteroid therapy at a dose equivalent of > 0.5 mg/kg of prednisone-equivalent per day - Concurrent use of other investigational anti-cancer agents - Chronic lymphocytic leukemia (CLL) or other active hematologic malignancy - Active uncontrolled infection: Human immunodeficiency virus (HIV) positive participants on highly active anti-retroviral therapy (HAART) with a CD4 count > 500 cells/mm^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have, per standard practice, hepatitis well-controlled on medication (e.g., AST and ALT < 5 x ULN) - Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Participants with small asymptomatic brain metastases (< 1 cm) or those with brain metastases previously treated with surgery or radiotherapy will be considered for inclusion at discretion of principal investigator, so long as other eligibility criteria are met. - For patients in phase 1/2, grade 3 or higher immune-mediated toxicity to any prior PD-L1 axis blocking agent - Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of up to 0.5 mg/kg prednisone per day, unless otherwise approved by PI - Study participants must not have significant active underlying neurologic disease, unless approved by PI. Neuropathy related to diabetes or prior chemotherapy is acceptable - Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI |
| 68 | NCT02006745 | completed | 1 | phase 3 | ['hiv'] | ["['B20', 'Z71.7', 'O98.72', 'Z21', 'O98.73', 'R75', 'Z11.4']"] | ['ribavirin', 'telaprevir'] | ['C1=NC(=NN1C2C(C(C(O2)CO)O)O)C(=O)N', 'CCCC(C(=O)C(=O)NC1CC1)NC(=O)C2C3CCCC3CN2C(=O)C(C(C)(C)C)NC(=O)C(C4CCCCC4)NC(=O)C5=NC=CN=C5'] | Inclusion Criteria: - 1. Is male or female aged 18 years or above 2. Has signed the Informed Consent Form voluntarily 3. Documented current acute hepatitis C genotype 1 infection with detectable HCV-RNA (PCR-assay) with an estimated duration less than 24 weeks as defined below: 1. HCV RNA positive AND 2. Prior negative anti-HCV antibody or HCV RNA test within 6 months OR 3. rise of liver transaminases above 2.5 x ULN within the past 6 months with prior normal transaminases during the year before AND 4. exclusion of other causes of acute hepatitis 4. Confirmed HIV infection 5. Receiving a atazanavir- or efavirenz- or raltegravir-based ART regimen or able to switch regimen to these agents with an undetectable HIV viral load for at least 3 months, or not receiving ART with no immediate plans to start ART during the first 6 months of study 6. CD4 T cell count >200/µl at screening in patients under ART, CD4 T cell count >500/µl at screening in patients without ART 7. If female and of childbearing potential, is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 4 months after the last dosage of ribavirin (ie 4 months after week 12, 24 or 48, depending on study arm and treatment response). Routine monthly pregnancy tests must also be performed during this time. Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential 8. Heterosexually active male participants or their female partners must use effective birth control methods (as agreed by the investigator) during the trial and for at least 7 months after the last dosage of ribavirin (ie 7 months after week 12, 24 or 48, depending on study arm and treatment response). Exclusion Criteria: - . HCV infection with non-1 genotype 2. Acute opportunistic infection requiring treatment 3. Malignancy requiring chemotherapy or radiotherapy 4. Active HBV infection (HBs Ag + with positive hepatitis B DNA) 5. Known autoimmune disease 6. Hepatic failure 7. History of ischaemic heart disease or other serious cardiac disease 8. Serious psychiatric disease which in the view of the investigator precludes the use of interferon 9. Haemoglobinopathy or severe anaemia of any cause 10. Serious abnormality on screening blood tests including, but not limited to: Hemoglobin <10g/dl, absolute neutrophil count <1000/mm3, platelets <90,000/mm3, creatinine clearance <60ml/min 11. If female, she is pregnant or breastfeeding 12. Known hypersensitivity to one of the trial drugs or its excipients 13. Other contraindicated concomitant treatment 14. Any condition (including drug/alcohol abuse), or laboratory results which in the investigators opinion, interfere with assessments or completion of the trial 15. Any other reason why, in the opinion of the investigator, the patient should not be enrolled in the trial. | |
| 69 | NCT02006472 | completed | 0 | phase 2 | ["huntington's disease"] | ["['G10']"] | ['pridopidine'] | ['CCCN1CCC(CC1)C2=CC(=CC=C2)S(=O)(=O)C'] | Inclusion Criteria: - Diagnosis of HD based on the presence of >/= 36 CAG repeats - Male or female age ≥21 years, with an onset of HD after 18 years' old. - Females of childbearing potential must be compliant in using adequate birth control throughout the duration of the study - Body weight ≥50 kg - Sum of >= 25 points on the UHDRS-TMS and UHDRS Independence Score <=90% - Able and willing to provide written informed consent prior to any study related procedure. - Willing to provide a blood sample for genetic analyses - Willing and able to take oral medication and able to comply with the study specific procedures. - Ambulatory, being able to travel to the study center, and judged by the investigator as likely to be able to continue to travel for the duration of the study. - Availability and willingness of a caregiver, informant or family member to accompany the patient to the clinic at study, and the suitability of the caregiver should be judged by the Investigator. - Other criteria apply, please contact the investigator for more information. Exclusion Criteria: - Patients with clinically significant heart disease at the screening visit - Treatment with tetrabenazine within 6 weeks of study screening - Patients with a history of epilepsy or of seizures within the last 5 years - Have other serious medical illnesses in the opinion of the investigator may put the patient at risk when participating in the study or may influence the results of the study or affect the patient's ability to take part in the study - Patients receiving medications (within the last 6 weeks prior to screening) that have been proven to prolong QT interval or who may require such medications during the course of the study such as but not limited to non allowed anti psychotic medications, tricyclic antidepressants and/or Class I antiarrhythmics - Other criteria apply, please contact the investigator for more information | |
| 70 | NCT02004366 | completed | 1 | phase 4 | ['type 2 diabetes'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['linagliptin', 'basal bolus', 'linagliptin', 'linagliptin + 50% glargine dose on discharge', 'linagliptin + 80% glargine'] | ['CC#CCN1C2=C(N=C1N3CCCC(C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C', 'CC#CCN1C2=C(N=C1N3CCCC(C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C'] | Inclusion Criteria: 1. Males or female surgical non-ICU patients ages between18 and 80 years 2. A known history of T2D > 1 month, receiving either diet alone, oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination therapy (excluding DPP-4 inhibitors) or low-dose (≤ 0.5 units/kg/day) insulin therapy. 3. Subjects with a BG >140 mg and < 400 mg/dL at time of randomization without laboratory evidence of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary ketones) Exclusion Criteria: 1. Age < 18 or > 80 years. 2. Subjects with increased BG concentration, but without a history of diabetes (stress hyperglycemia). 3. Subjects with a history of type 1 diabetes (suggested by BMI < 25 requiring insulin therapy or with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria) (43). 4. Treatment with dipeptidyl peptidase-4 (DPP4) inhibitor or Glucagon-like peptide-1 (GLP1) analogs during the past 3 months prior to admission. 5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit. 6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction. 7. Patients with clinically relevant pancreatic or gallbladder disease. 8. Patients with previous history of pancreatitis 9. Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR < 30 ml/min). 10. Chronic use of steroid with total daily dose (prednisone equivalent) >5 mg/day 11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. 12. Pregnancy or breast feeding at time of enrollment into the study. 13. Patients who received supplemental sliding scale insulin >72 hours prior to randomization 14. Patients who received basal insulin > 48 hours prior to randomization | |
| 71 | NCT02000622 | active, not recruiting | 1 | phase 3 | ['breast cancer metastatic', 'brca 1 gene mutation', 'brca 2 gene mutation'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['D68.52', 'J84.83']", "['D68.52', 'J84.83']"] | ['olaparib', "physician's choice chemotherapy"] | ['C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F'] | Inclusion Criteria: - Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious. - Histologically or cytologically confirmed breast cancer with evidence of metastatic disease. - Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting. - Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed. - ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy. - ECOG performance status 0-1. - Adequate bone marrow, kidney and liver function. Exclusion Criteria: - Prior treatment with PARP inhibitor. - Patients with HER2 positive disease. - More than 2 prior lines of chemotherapy for metastatic breast cancer. - Untreated and/or uncontrolled brain metastases. - Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed. - Known HIV (Human Immunodeficiency Virus) infection. - Pregnant or breast-feeding women. | |
| 72 | NCT02006121 | completed | 1 | phase 3 | ["parkinson's disease"] | ["['G20']"] | ['apomorphine hydrochloride', 'placebo'] | ['CN1CCC2=C3C1CC4=C(C3=CC=C2)C(=C(C=C4)O)O.Cl'] | Inclusion Criteria: - Male or female patients aged ≥30 years - Diagnosis of idiopathic PD of >3 years' duration, defined by the UK Brain Bank criteria (with the exception of >1 affected relative being allowed), without any other known or suspected cause of Parkinsonism - Hoehn & Yahr stage up to 3 in the ON and 2 to 5 in the OFF state - Motor fluctuations not adequately controlled on medical treatment including levodopa which was judged by the treating physician to be optimal - Average of OFF time > 3 hours/day based on screening and baseline diary entries with no day with < 2 hours of OFF time recorded - Stable medication regimen, with a stable dose of levodopa administered in at least 4 intakes, for at least 28 days prior to baseline. All oral or transdermal antiparkinsonian drugs were permitted, with the exception of budipine. This regimen might include the use of levodopa/DDCI rescue medication, if this occurred up to 2 times a day, at doses of up to 200 mg levodopa/day - Patients must be able to differentiate between the ON and OFF state and between troublesome and non-troublesome dyskinesias - Male and female patients must be compliant with a highly effective contraceptive method (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method) during the study and for the 12-month OLP, if sexually active - Females of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) or urine pregnancy test at screening - Ability to accurately complete a paper diary on designated days (with assistance from caregivers, if required), recording periods when they are "ON without troublesome dyskinesia", "ON with troublesome dyskinesia", OFF, and sleeping - Written informed consent prior to enrolment, after being provided with detailed information about the nature, risks, and scope of the clinical trial as well as the expected desirable and adverse effects of the study treatments - Patients considered reliable and capable of adhering to the protocol, visit schedule, and medication intake according to the judgment of the investigator Exclusion Criteria: - History of respiratory depression - Hypersensitivity to apomorphine or any excipients of the medicinal product - High suspicion of other parkinsonian syndromes - Presence of severe freezing or clinically relevant postural instability leading to falls during the ON state - Concomitant therapy or within 28 days prior to baseline with: apomorphine pen injections; alpha-methyl dopa, metoclopramide, reserpine, neuroleptics, methylphenidate, or amphetamine; intrajejunal levodopa - Previous use of apomorphine pump treatment - History of deep brain stimulation or lesional surgery for PD - Any medical condition that is likely to interfere with an adequate participation in the study, including e.g. current diagnosis of unstable epilepsy; clinically relevant cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months - Symptomatic, clinically relevant and medically uncontrolled orthostatic hypotension - Patients with a borderline QT interval corrected for heart rate according to Bazett's formula (QTcB) of >450 msec for male and >470 msec for female at screening or history of long QT syndrome; or >450 msec absolute duration - Clinically relevant hepatic dysfunction (total bilirubin >2.0 mg/dL, alanine transaminase [ALT] and aspartate transaminase [AST] >2 times the upper limit of normal) - Clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL) - Pregnant and breastfeeding women - Clinically relevant cognitive decline, defined as MMSE ≤24 or according to Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria for dementia - Active psychosis or history of at least moderate psychosis in the past year, or with medically uncontrolled severe depression; very mild illusions or hallucinations in the sense of "feelings of passage or presence" with fully retained insight are not an exclusion criterion - Known history of melanoma - Any investigational therapy in the 4 weeks prior to randomization - History or current drug or alcohol abuse or dependencies | |
| 73 | NCT02005471 | completed | 1 | phase 3 | ['chronic lymphocytic leukemia'] | ["['C91.11', 'C91.12', 'C91.10']"] | ['bendamustine', 'venetoclax', 'rituximab'] | ['CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCC(=O)O', 'CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C'] | Inclusion Criteria: - Diagnosis of CLL per diagnostic criteria for relapsed or refractory CLL per the international workshop on chronic lymphocytic leukemia (iwCLL) guidelines - Previously treated with 1-3 lines of therapy (example: completed greater than or equal to [>/=] 2 treatment cycles per therapy), including at least one standard chemotherapy-containing regimen - Participants previously treated with bendamustine only if their duration of response was >/= 24 months - Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 1 - Adequate bone marrow function - Adequate renal and hepatic function - Participants must use effective birth control throughout study until at least 30 days after study treatment or 1 year after rituximab treatment, whichever is later; female participants must not be pregnant or breast-feeding - For participants with the 17p deletion, previously treated with 1-3 lines of therapy, including at least one prior standard chemotherapy-containing regimen or at least one prior alemtuzumab-containing therapy Inclusion Criteria R/C Substudy: - Participants randomized to Arm A or Arm B with a confirmed disease progression of CLL per iwCLL criteria - Participants who have not received new anti-CLL therapy following disease progression in Arm A or Arm B - Adequate renal and hepatic function per laboratory reference range Exclusion Criteria: - Transformation of CLL to aggressive non-Hodgkin lymphoma or central nervous system (CNS) involvement by CLL - Undergone an allogenic stem cell transplant - A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular or hepatic disease - Hepatitis B or C or known human immunodeficiency virus (HIV) positive - Receiving warfarin treatment - Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug - Received any anti-cancer or investigational therapy within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy - Received cytochrome P450 3A4 (CYP3A4) inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamazapine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax - History of prior venetoclax treatment - Participants with another cancer, history of another cancer considered uncured on in complete remission for <5 years, or currently under treatment for another suspected cancer except non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated or excised and is considered resolved - Malabsorption syndrome or other condition that precludes enteral route of administration - Other clinically significant uncontrolled condition(s) including, but not limited to, systemic infection (viral, bacterial or fungal) - Vaccination with a live vaccine within 28 days prior to randomization - Consumed grapefruit or grapefruit products, seville oranges (including marmalade containing seville oranges), or star fruit within 3 days prior to the first dose of study treatment - A cardiovascular disability status of New York Heart Association Class >/=3. Class 3 is defined as cardiac disease in which participants are comfortable at rest but have marked limitation of physical activity due to fatigue, palpitations, dyspnea, or anginal pain - Major surgery within 30 days prior to the first dose of study treatment - A participant who is pregnant or breastfeeding - Known allergy to both xanthine oxidase inhibitors and rasburicase Exclusion Criteria R/C Substudy: - Transformation of CLL to aggressive NHL (e.g., Richter's transformation, prolymphocytic leukemia, or DLBCL) or CNS involvement by CLL - Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) - Development of other malignancy since enrollment into the study, with the exception of curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix - Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia - History of severe (i.e., requiring permanent discontinuation of prior rituximab therapy) prior allergic or anaphylactic reactions to rituximab - Known HIV positivity - Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HbsAg] serology) - Positive test results for hepatitis C virus (HCV; HCV antibody serology testing) - Requires the use of warfarin (due to potential drug interactions that may potentially increase the exposure of warfarin) - Has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy - Received potent CYP3A4 inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of study treatment - Received potent CYP3A4 inducers (such as rifampin, carbamazepine, phenytoin, St. John's wort) within 7 days prior to the first dose of study treatment - Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study treatment - A cardiovascular disability status of New York Heart Association Class >/= 3 - A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the participants's participation in this study or interpretation of study outcomes - Major surgery within 30 days prior to the first dose of study treatment - A participant who is pregnant or breastfeeding - Malabsorption syndrome or other condition that precludes enteral route of administration - Known allergy to both xanthine oxidase inhibitors and rasburicase - Vaccination with a live vaccine within 28 days prior to randomization | |
| 74 | NCT02008227 | completed | 1 | phase 3 | ['non-squamous non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['atezolizumab', 'docetaxel'] | ['CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)O)C)O'] | Inclusion Criteria: - Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) NSCLC - Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens - Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen or combined modality (e.g., chemoradiation) regimen with curative intent - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: - Known active or untreated central nervous system (CNS) metastases - Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome - History of autoimmune disease - History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted - Active hepatitis B or hepatitis C - Prior treatment with docetaxel - Prior treatment with cluster of differentiation 137 (CD137) agonists, anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents | |
| 75 | NCT02008318 | completed | 0 | phase 2/phase 3 | ['myelodysplastic syndromes'] | ["['D46.9', 'D46.C', 'D46.Z']"] | ['galunisertib', 'placebo'] | ['CC1=NC(=CC=C1)C2=NN3CCCC3=C2C4=C5C=C(C=CC5=NC=C4)C(=O)N'] | Inclusion Criteria: - Confirmed diagnosis of MDS based on the World Health Organization (WHO) criteria - Participants with 5q deletions are allowed only if they have failed or are intolerant of lenalidomide treatment - Participants must have a Revised International Prognostic Scoring System (IPSS-R) category of very low-, low-, or intermediate-risk disease - In the 8 weeks prior to registration, participants in phase 2 should have anemia with Hb ≤10.0 g/dL (based on the average of 2 baseline measurements and untransfused for at least 1 week) with or without red blood cell (RBC) transfusion dependence confirmed for a minimum of 8 weeks before enrollment - For phase 3, participants should have anemia with RBC transfusion dependence confirmed within 8 weeks before enrollment - Performance status ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - No history of moderate or severe cardiac disease - No prior history of acute myeloid leukemia (AML) | |
| 76 | NCT02000531 | completed | 1 | phase 4 | ['carcinoma, non-small-cell lung'] | ["['D02.20', 'D02.21', 'D02.22']"] | ['erlotinib', 'chemotherapy'] | ['COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC'] | Inclusion Criteria: - Participant in ENSURE trial - Disease progression during first-line treatment Exclusion Criteria: - N/A | |
| 77 | NCT04270929 | withdrawn | insufficient accrual rate | 0 | phase 1 | ['pancreatic adenocarcinoma'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['folfiri', 'folfirinox'] | ['CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)OC(=O)N6CCC(CC6)N7CCCCC7.C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O.C1=C(C(=O)NC(=O)N1)F', 'CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)OC(=O)N6CCC(CC6)N7CCCCC7.C1CCC(C(C1)[NH-])[NH-].C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O.C1=C(C(=O)NC(=O)N1)F.C(=O)(C(=O)[O-])[O-].[Pt+4]'] | Inclusion Criteria: - Patient with histologically confirmed diagnosis of adenocarcinoma of the pancreas. Patient must have either histologic confirmation of the primary tumor or metastasis. - Patients must have locally advanced, unresectable or metastatic pancreatic adenocarcinoma. - Patient must be between 18 - 80 years of age. - Patient able to understand and sign informed consent. - Patient may be chemotherapy naïve or may have failed one line of conventional therapy - Prior FOLFIRINOX therapy: - Patients who have previously received FOLFIRINOX chemotherapy for locally advanced unresectable pancreatic cancer are eligible for enrollment upon this study if they meet the following criteria- 1. FOLFIRINOX chemotherapy was completed more than six months ago, 2. Patients who are currently candidates for re-challenge with FOLFIRINOX chemotherapy for their recurrent cancer, and 3. Patients have no persistent non-hematologic toxicity greater than grade 1 (due to prior FOLFIRINOX therapy) - Patients with metastatic cancer who are currently receiving FOLFIRINOX chemotherapy are eligible for enrollment upon this study if they meet the following criteria- 1. Patients have received no more than six cycles of FOLFIRINOX chemotherapy, 2. Patients have at least stable disease on imaging, and 3. Patients have no persistent non-hematologic toxicity greater than grade 1 (due to ongoing FOLFIRINOX therapy) - Patient with a life expectancy of greater than six months. - Patient with performance status of 0 to 1 (ECOG). - All patients must have adequate organ function as defined by: - ANC greater than or equal to 1500/mm3, platelets ≥ 100,000/mm3, Hgb ≥ to 8 g/dL; patient may be transfused to achieve Hgb ≥ 8 g/dL to satisfy enrollment criteria, or as otherwise indicated by symptoms for Hgb > 8 g/dL. - Creatinine ≤ 1.5mg/dl or creatinine clearance ≤ 60cc/min. - Direct bilirubin <1.5X ULN, alkaline phosphatase <5X ULN, and ALT/AST <5X ULN (ULN = upper limit of normal). - No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias, including uncontrolled atrial fibrillation/atrial flutter, evidence of prior myocardial infarction by history or EKG. - No serious, symptomatic obstructive or emphysematous lung disease, or asthma requiring intravenous medications within the past 12 months; no serious lung disease associated with dyspnea at normal activity levels (grade III) or at rest (grade IV), due to any cause (including cancer metastases and pleural effusions). - Acceptable vascular anatomy as determined by CT, MR, or conventional venography. Exclusion Criteria: - Female patients of childbearing age will be tested for pregnancy. Pregnant and breastfeeding patients will be excluded from the study. Males who are actively seeking to have children will be made aware of the unknown risks of this study protocol on human sperm and the need to practice birth control. - Patients with serious or unstable renal, hepatic, pulmonary, cardiovascular, endocrine, rheumatologic, or allergic disease based on history, physical exam and laboratory tests will be excluded. - Patients with uncontrolled diabetes mellitus or a history of pancreatitis. - Patients with cholelithiasis and a history of choledocholithiasis. - Patients with concurrent malignancies, except for cutaneous carcinomas. - Patients with unsuitable vascular anatomy. - Portal vein occlusion/thrombosis, history of portal hypertension, cirrhosis, hepatitis, or with radiographic evidence of cirrhosis. |
| 78 | NCT04279561 | terminated | slow accrual | 0 | phase 1 | ['castration-resistant prostate carcinoma', 'metastatic prostate carcinoma', 'stage iv prostate cancer american joint committee on cancer (ajcc) v8', 'stage iva prostate cancer ajcc v8', 'stage ivb prostate cancer ajcc v8'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['gallium ga 68 gozetotide'] | ['[H+].C1=CC(=C(C=C1CCC(=O)NCCCCCC(=O)NCCCCC(C(=O)O)NC(=O)NC(CCC(=O)O)C(=O)O)CN(CCN(CC2=C(C=CC(=C2)CCC(=O)O)[O-])CC(=O)[O-])CC(=O)[O-])[O-].[Ga+3]'] | Inclusion Criteria: - Histologically proven prostate cancer - Know metastatic disease on previous imaging, or PSA value ⩾ 1 ng/ml; - Castration resistant disease with confirmed testosterone level =< 50 ng/ml under prior first-line androgen deprivation therapy (ADT) - New planned treatment with enzalutamide or abiraterone, darolutamide or apalutamide - Willingness to undergo ARSI throughout the duration of the study as prescribed by the treating uro-oncologist - Stated willingness to comply with continuation of ARSI treatment for the duration of the study - Provision of signed and dated informed consent form Exclusion Criteria: - Inability to provide written informed consent - Known inability to remain still and lie flat for duration of each imaging procedure (about 30 minutes) - Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy - A baseline superscan pattern on bone scan - Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible |
| 79 | NCT02030483 | terminated | the company providing one of the study drugs withdrew its support due to low enrollment. therefore, we had to close the study due to lack of funding. | 0 | phase 1 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['palbociclib', 'dexamethasone', 'lenalidomide'] | ['CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C', 'CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C', 'C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3N'] | Inclusion Criteria: - Subject must voluntarily sign and understand written informed consent. - Subject is ≥18 years at the time of signing the consent form. - Subject has histologically confirmed multiple myeloma that expresses phosphorylated retinoblastoma protein (pRb), as assessed using a historical biopsy sample if available, or a freshly obtained tumor sample. - Subject has relapsed or refractory myeloma as defined by progression of disease either after prior therapy or lack of response to currently used therapy. - Subject must have received and relapsed or progressed after prior treatment with bortezomib. - Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI. - Subject has a Karnofsky performance status ≥60% (>50% if due to bony involvement of myeloma - Subject is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin). - Subject is registered into the mandatory Revlimid REMS®program, and is willing and able to comply with the requirements of Revlimid REMS® program. - If subject is a female of childbearing potential (FCBP), she must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. Men must agree to continue birth control for 90 days post-last dose of PD-0332991 - All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program. - Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. - Subject has a life expectancy ≥ 3 months - Subjects must meet the following laboratory parameters: - Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) - Platelet count ≥ 75,000/mm3 (75 x 109/L) - Serum SGOT/AST <3.0 x upper limits of normal (ULN) - Serum SGPT/ALT <3.0 x upper limits of normal (ULN) - Serum creatinine clearance, (either calculated or directly measured). ≥ 60cc/min - Serum total bilirubin <2.0 mg/dL (34 μmol/L) Exclusion Criteria: - Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning). - Subject has a prior history of other malignancies unless disease free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels. - Subject has had myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. - Female subject who is pregnant or lactating. - Subject has known HIV infection - Subject has known active hepatitis B or hepatitis C infection. - Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program. - Subject has known hypersensitivity to dexamethasone or lenalidomide. - Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment. - Subject has any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent. - Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. |
| 80 | NCT02032875 | completed | 1 | phase 3 | ['hepatitis c'] | ["['B18.2', 'B17.10', 'B17.11', 'B19.20', 'B19.21', 'B15.0', 'B15.9']"] | ['daclatasvir', 'sofosbuvir', 'ribavirin'] | ['CC(C)C(C(=O)N1CCCC1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)C6CCCN6C(=O)C(C(C)C)NC(=O)OC)NC(=O)OC', 'CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3', 'C1=NC(=NN1C2C(C(C(O2)CO)O)O)C(=O)N'] | For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: - Participants must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications - Participants chronically infected with hepatitis C virus (HCV) Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥10,000 IU/mL at screening - Participants may be treatment-naïve or treatment-experienced - Cirrhotic participants must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol - Post-transplant participants must be at least 3 months post-transplant with no evidence of moderate or severe rejection Exclusion Criteria: - History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited - Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening - Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures) - History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Participants with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative) - Active hospitalization for decompensated liver disease | |
| 81 | NCT02034513 | completed | 1 | phase 3 | ['diabetes', 'diabetes mellitus, type 1'] | ["['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']", "['E10.65', 'E10.9', 'E10.21', 'E10.36', 'E10.41', 'E10.42', 'E10.44']"] | ['insulin degludec', 'insulin glargine', 'insulin aspart'] | ['Status: 503', 'CCC(C)C1C(=O)NC2CSSCC(C(=O)NC(CSSCC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)NCC(=O)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC7=CC=C(C=C7)O)C(=O)NC(C(C)O)C(=O)N8CCCC8C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCNC(=N)N)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)C(CC(C)C)NC(=O)C(CC2=CNC=N2)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC2=CC=CC=C2)N)C(=O)NC(C(=O)NC(C(=O)N1)CO)C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C(C)CC)NC(=O)CN', 'CCC(C)C1C(=O)NC2CSSCC(C(=O)NC(CSSCC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)NC(CC(=O)N)C(=O)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC7=CC=C(C=C7)O)C(=O)NC(C(C)O)C(=O)NC(CC(=O)O)C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)O)C(C)C)CC(C)C)CC8=CC=C(C=C8)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC9=CNC=N9)CO)NC(=O)C(CC(C)C)NC(=O)C(CC2=CNC=N2)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC2=CC=CC=C2)N)C(=O)NC(C(=O)NC(C(=O)N1)CO)C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C(C)CC)NC(=O)CN'] | Inclusion Criteria: - Subjects fulfilling at least one of the below criteria: a) Experienced at least one severe hypo episode within the last year (according to the ADA (American Diabetes Association) definition, April 2013) b) Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m^2 per CKD-Epi (chronic kidney disease epidemiology collaboration) c) Hypoglycaemic symptom unawareness d) Diabetes mellitus duration for more than 15 years e) Recent episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (below or equal to 70 mg/dL [below or equal to 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening) - Male or female, age at least 18 years at the time of signing informed consent - Type 1 diabetes mellitus (diagnosed clinically) for at least 52 weeks prior to Visit 1 - Current treatment with a basal-bolus regimen consisting of neutral protamine Hagedorn (NPH) insulin OD (once daily) / BID (twice daily) or insulin detemir (IDet) OD / BID plus 2-4 daily injections of any rapid acting meal time insulin or CSII (with rapid acting insulin) for at least 26 weeks prior to Visit 1 - HbA1c (glycosylated haemoglobin) below or equal to 10% by central laboratory analysis - BMI (body mass index) below or equal to 45 kg/m^2 Exclusion Criteria: - Treatment with IGlar or IDeg within the last 26 weeks prior to Visit 1 (short term use [less than or equal to 2 weeks] is allowed, but not within 4 weeks prior to screening) - Use of any other anti-diabetic agent than those stated in the inclusion criteria within the last 26 weeks prior to Visit 1 | |
| 82 | NCT02038452 | completed | 1 | phase 4 | ['carpal tunnel syndrome (cts)'] | ["['D68.61', 'D69.41', 'D81.4', 'E24.1', 'E26.01', 'E26.81', 'E34.0']"] | ['depo-medrone'] | ['CC1CC2C3CCC(C3(CC(C2C4(C1=CC(=O)C=C4)C)O)C)(C(=O)COC(=O)C)O'] | Inclusion Criteria: - Male or female aged ≥ 18 years - A clinical diagnosis of unilateral or bilateral CTS as made by a GP or trained clinician according to the diagnostic criteria - Mild (e.g. intermittent paraesthesia) or moderate (e.g. constant paraesthesia, reversible numbness and / or pain) severity CTS of idiopathic nature - Symptom duration of episode of at least 6 weeks - Written informed consent provided by the patient, prior to any trial specific procedures Exclusion Criteria: - Steroid injection or night splints for CTS in the affected wrist within preceding 6 months - Any previous surgery on the affected wrist - Severe CTS exhibiting constant numbness or pain, constant sensory loss, severe thenar muscle atrophy or symptom severity which requires the patient to be referred for a surgical opinion - Clinical suspicion of local or systemic sepsis or infection - Current or previous infection of the affected wrist - Trauma to the affected hand requiring surgery or immobilisation in the previous 12 months - Unable to tolerate the study interventions - Unable to understand and complete self-report questionnaires written in English - Inter-current illness including, but not limited to: - poorly controlled thyroid disease - poorly controlled diabetes mellitus - vibration-induced neuropathy - inflammatory joint disease - suspected complex neurological conditions - any other severe medical illness which in the opinion of the local Principal Investigator (or other authorised clinical delegate) precludes trial participation - Pregnant or lactating females - Receiving anticoagulants - Any history of hypersensitivity to Depo-Medrone or any of its excipients - Allergy to any of the splint materials - Known abuse of drugs or alcohol - Involved in on-going litigation cases for their condition | |
| 83 | NCT02038036 | completed | 1 | phase 3 | ['polycythemia vera'] | ["['D45']"] | ['best available therapy', 'ruxolitinib'] | ['C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3'] | Inclusion Criteria: Confirmed diagnosis of PV according to the 2008 World Health Organization criteria, Non-palpable spleen, Phlebotomy dependent, Resistant to or intolerant of hydroxyurea, ECOG performance status of 0, 1 or 2. Exclusion Criteria: Inadequate liver or renal function, Significant bacterial, fungal, parasitic, or viral infection requiring treatment, Active malignancy within the past 5 years, excluding specific skin cancers, Previously received treatment with a JAK inhibitor, Being treated with any investigational agent, Women who are pregnant or nursing. Other inclusion/exclusion criteria apply. | |
| 84 | NCT02039050 | completed | 1 | phase 4 | ['pulmonary disease, chronic obstructive'] | ["['J44.9', 'J44.1', 'J44.0']"] | ['tiotropium', 'aclidinium'] | ['C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C', 'C1C[N+]2(CCC1C(C2)OC(=O)C(C3=CC=CS3)(C4=CC=CS4)O)CCCOC5=CC=CC=C5'] | Inclusion Criteria: - Male and female volunteers aged 40-80 years with moderate to severe COPD (GOLD Stage 2, 3). - On inhaled corticosteroids / long-acting beta agonists - FEV1 30-80% predicted and FEV1/FVC <70%. - Smoking history ≥10 pack-years. - Ability to give informed consent - Agreement for their General Practitioner to be made aware of study participation and to receive feedback as relevant to the participant's well being Exclusion Criteria: - Other respiratory diseases such as asthma, bronchiectasis or allergic bronchopulmonary aspergillosis - A COPD exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement (3 months if hospitalisation has been required) - Any clinically significant medical condition that may endanger the health or safety of the participant - Known or suspected sensitivity to/intolerance of investigational medicinal product - Patients with prostatic hyperplasia, bladder outflow obstruction or glaucoma - Pregnancy or lactation - Unable to comply with the procedures of the protocol | |
| 85 | NCT02034292 | terminated | sponsor decision | 0 | phase 1 | ['acute coronary syndrome'] | ["['I24.0']"] | ['clopidogrel', 'aspirin', 'apd791', 'placebo'] | ['COC(=O)C(C1=CC=CC=C1Cl)N2CCC3=C(C2)C=CS3', 'CC(=O)OC1=CC=CC=C1C(=O)O', 'CN1C(=CC=N1)C2=C(C=CC(=C2)NC(=O)C3=CC(=CC=C3)OC)OCCN4CCOCC4'] | Inclusion Criteria: 1. a healthy adult between 20 and 45 years old at the time of visit for screening 2. a person who is able to give written consent 3. a person between 50 and 85 kg at the time of visit for screening 4. a woman who is negative on a serum hCG test at the time of visit and the day before a trial, and who is not nursing 5. a woman who agrees on double contraception, medically approved, from the time of visit for screening to 90 days after the last administration of a clinical trial drug, or who had a contraceptive operation no later than 120 days before visit for screening, or who is menopausal 6. a man who had a contraceptive operation no later than 120 days before visit for screening, or who agrees on double contraception, medically approved, from the time of visit for screening to 90 days after the last administration of a clinical trial drug, and also agree not to donate sperm 7. a person more than hemoglobin 12 g/dL at the time of screening (a woman more than hemoglobin 11 g/dL) 8. a person whose vital signs were in the normal range at the time of visit for screening, or who is medically determined not to be clinically significant by an investigator 9. a person who voluntarily decides to participate in this clinical trial and gives written consent on strict clinical trial compliance 10. a person whose blood can be collected during a study period with visit for monitoring Exclusion Criteria: 1. a person with the medical history of gastric ulcer, duodenal ulcer or esophageal ulcer within 90 days from the time of visit for screening 2. a person with the medical history of gastrointestinal diseases(e.g. Crohn's disease, ulcerative colitis, etc.) or surgery(excluding uncomplicated appendectomy or herniotomy) affecting the absorption of a clinical trial drug 3. a person with the medical history of blood coagulation disorder or hemorrhagic diseases, or with clinically significant abnormal findings decided by a investigator on blood coagulation test at the time of screening 4. a woman with the medical history of dysfunctional uterine bleeding within a year from the time of visit for screening 5. a person with the medical history of epilepsy or convulsion 6. a person with the medical history of internal organ transplant 7. a person expected to be hard to complete a clinical trial because of surgery or medical procedures planned within a clinical trial period 8. a person with the medical history of clinically significant new diseases within 30 days from the time of visit for screening according to investigator's decision 9. a person with hypersensitivity reaction to a drug or gelatin, or the medical history of clinically significant hypersensitivity reaction 10. a person with the history of drug abuse, or with a positive reaction to a drug possible to be abused on urine drug screening 11. a person with the medical history of alcohol abuse within two years from the time of visit for screening 12. a person who is a smoker, or with a positive reaction on a urine nicotine test conducted at the time of visit for screening 13. a person who donated whole blood within 60 days or constituents of blood within 30 days, or received a blood transfusion within 30 days from the time of visit for screening 14. a person taking other clinical trial drugs within 90 days from the time of visit for screening 15. a person taking a prescription drug within 30 days, or a contraindicated drug or oriental medicine within 14 days from the time of visit for screening 16. a person with a positive reaction to a serum test(hepatitis B test, hepatitis C test, HIV test, syphilis test) 17. a person with hepatic enzymes(AST, ALT) more than 2.5 times of the reference upper limit(UNL) or total bilirubin more than 1.5 times of the reference upper limit(UNL) or creatinine more than 1.25 times of the reference upper limit(UNL) 18. a person expected to be hard to complete a clinical trial due to physical or mental status according to investigator's medical decision at the time of visit for screening 19. a person decided to be inappropriate to participate in this clinical trial according to investigator's medical decision on the result of laboratory tests, such as complete blood cell count, general chemical test, clinicochemical urinalysis, and physical examination, vital signs, ECG, other tests excluding exclusion criteria 17 items conducted before subject selection for a clinical trial |
| 86 | NCT02037503 | unknown status | 1 | phase 3 | ['suicidal ideation', 'major depressive disorder', 'healthy participants'] | ["['R45.851']", "['F33.0', 'F33.1', 'F33.9', 'F32.0', 'F32.1', 'F32.9', 'F33.40']"] | ['ketamine', 'saline'] | ['CNC1(CCCCC1=O)C2=CC=CC=C2Cl', '[Na+].[Cl-]'] | Inclusion Criteria: Suicidal Ideation group: 1. Any person admitted to the emergency room department after a suicide attempt , defined as requiring medical intervention - not just a psychiatrist ( surgical or pharmacological treatment but also the need for observation ) . 2. The need for medical intervention will be defined by the ER ED physician 3. Ages 18-65 For the depression group: 1. Diagnosed with major depression according to DSM VI. 2. Ongoing depression (according to DSM criteria) despite treatment with at least two antidepressants in adequate dosages and for longer than three weeks. 3. Ages 18-65 For the romantic relationship breakup: 1. Participants that have experienced a meaningful romantic relationship break-up within the past 12 months - Exclusion Criteria for all groups: 1. Psychotic state instate in the examination 2. Diagnosis of schizophrenia / schizoaffective disorder 3. Drug or alcohol abuse as is revealed in by blood/urine tests 4. Patient in which, according to the examiner, there is primary or secondary gain. 5. Patient , which, at the time of his admission , is without any pharmacological treatment. | |
| 87 | NCT02033369 | completed | 1 | phase 4 | ['major depressive disorder'] | ["['F33.0', 'F33.1', 'F33.9', 'F32.0', 'F32.1', 'F32.9', 'F33.40']"] | ['pramipexole'] | ['CCCNC1CCC2=C(C1)SC(=N2)N'] | Inclusion Criteria: - Weight between 44 kg and 115 kg - Meets DSM-IV criteria for principal diagnosis of MDD, current major depressive episode, without psychotic features - Score of >16 and <29 on 17-item Hamilton Rating Scale for Depression - Psychotropic-naïve, as defined by lifetime <2 weeks treatment with antidepressants, anxiolytics or antipsychotics - Able to tolerate a treatment-free period during study participation - Able to provide informed consent Exclusion Criteria: - A principal diagnosis of any current Axis I psychiatric disorder other than the MDD - Lifetime diagnosis of any psychotic disorder, bipolar disorder, mental retardation, attention deficit/hyperactivity disorder, or substance use disorders (including nicotine use disorders) - Serious suicidal risk or history of violent behavior which would make participation in the protocol unsafe - Any tobacco use in the prior three months (if not already excluded for abuse/dependence by #1) - Illicit drug use in the prior three months, as evidenced by history or urine toxicology screen - Women who are pregnant, nursing, postmenopausal, or using hormonal methods of birth control - Women who are not using an effective birth control method or sexual abstinence during the ten days before the scan - Any medical or neurological problem that might affect interpretation of findings or safety of participation (e.g., blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, malignancy, neurological diseases of the brain, history of seizures or head trauma), low hemoglobin (Hb < 12 gm/dL in males, Hb < 10.5 gm/dL in females)) - Blood donation within 4 weeks of study - Metal implants or paramagnetic objects in the body that might affect safety of undergoing MRI (e.g., heart pacemaker, shrapnel, bullets, surgical prostheses or surgical clips), as determined in consultation with a neuroradiologist and according to the guidelines set forth in the reference: "Guide to MR procedures and metallic objects" Shellock; Lippincott Williams and Wilkins, NY, 2001 - More than one major risk factor for coronary artery disease (e.g. hyperlipidemia, sedentary lifestyle). Smokers are already excluded by #4 above, and diabetics by #8 above - Systolic blood pressure > 140 or diastolic blood pressure > 90 based on at least two readings at rest - History of untoward reaction to amphetamine or other stimulant medication, or pramipexole - Any psychotropic treatment in the past 3 weeks (or depot medication in the past 6 months), except for lorazepam,which may be administered as needed prior to imaging day - Current, past or anticipated exposure to radiation in the workplace, or participation in nuclear medicine procedures, including research protocols (In case of previous exposure to activity due to research studies, subjects will be eligible if all conditions listed below are fulfilled: 1) The injected dose and dosimetry of the radiotracer are known; 2) Except for research studies, the subject has not been exposed to radiation (workplace and medical); 3) Adding prior exposure to the exposure due to the study will result in a yearly cumulative exposure lower than the FDA limit for research studies - Family history of schizophrenia in parents, siblings, or children - Ongoing cognitive-behavioral or interpersonal psychotherapy for depression (Supportive therapy is not an exclusion) - Ongoing treatment with cimetidine | |
| 88 | NCT02031081 | completed | 0 | phase 2/phase 3 | ['gastroparesis', 'diabetes mellitus'] | ["['K31.84']", "['P70.2', 'O24.92', 'Z83.3', 'E10.65', 'E10.9', 'E11.65', 'E11.9']"] | ['prucalopride', 'placebo'] | ['COCCCN1CCC(CC1)NC(=O)C2=CC(=C(C3=C2OCC3)N)Cl'] | Inclusion Criteria: - Age of 18-64 years - Existing clinical diagnosis of gastroparesis for at least one year as judged by the study gastroenterologist based on past medical history, clinical symptoms - Sufficiently symptomatic at time of proposed study (Minimum baseline postprandial satiety/fullness subscale of the Gastroparesis Cardinal Symptoms Index (GCSI) score of 1.5 or higher) - Delayed gastric emptying (>10% retention at 4 hours) on standard solid meal scintigraphic emptying study within the previous year - Normal upper endoscopy (with the exception of small bezoars) since the onset of symptoms - If female of childbearing potential, a negative urine pregnancy test administered between consent and screening appointments - Able to provide written informed consent Exclusion Criteria: - Clinical evidence (including physical exam and/or ECG) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns, including pregnancy or breastfeeding. - Study entry ECG showing second or third degree heart block, left bundle branch block (LBBB) or acute ischemic changes - Blood electrolytes (Na, K, CL) measured within past 6 months outside of normal reference ranges (except during an acute gastroparesis flare-up) - Use of narcotics or promotility agents which cannot be stopped prior to study entry. - Use of tricyclic antidepressants (at doses exceeding 25 mg/day) and/or macrolide antibiotics. (Stable doses of SSRI/SNRI antidepressants and/or non-macrolide antibiotics are permitted) - Laxative use that cannot be stopped prior to the start of the study - Participated in clinical trial with motility agents within past 30 days - History of gastrointestinal surgery excepting appendectomy and/or cholecystectomy in the past, or any other major surgeries within 3 months - Estimated GFR<30 measured within past 6 months. - History of cardiovascular disorder including myocardial infarction, pacemaker or implanted defibrillator, or history of life-threatening arrhythmia | |
| 89 | NCT02038179 | completed | 0 | phase 2/phase 3 | ['pre-hypertension', 'jnc 7 stage i hypertension'] | ["['O11.1', 'O11.2', 'O11.3', 'O11.4', 'O11.9', 'O11.5', 'O10.02']", "['I15.0', 'I97.3', 'K76.6', 'P29.2', 'G93.2', 'H40.053', 'I10']"] | ['allopurinol', 'placebo'] | ['C1=NNC2=C1C(=O)NC=N2'] | Inclusion Criteria: - Pre-hypertension or stage I hypertension, defined as the following after the mean of two clinic measurements: - Systolic blood pressure (SBP) ≥ 120 and <160 or; - Diastolic blood pressure (DBP) ≥ 80 and < 100 - Serum urate ≥ 5.0 mg/dL for men or ≥ 4.0 mg/dL for women - Age 18-40 Exclusion Criteria: - Any current pharmacological treatment for hypertension, including diuretics (calcium channel blockers at stable doses were later allowed) - Estimated glomerular filtration rate < 60 mL/min/1.73m2 - Current use of any urate-lowering therapy or statins - Prior diagnosis of gout or past use of urate-lowering therapy for gout - Prior diagnosis of diabetes - Pregnancy, or recent delivery or last trimester pregnancy loss more recent than 3 months - Active smokers - Immune-suppressed individuals including transplant recipients or current use of azathioprine. - Leucopenia with absolute white cell count < 3000 /mL, anemia with hemoglobin < 12 g/dL, or thrombocytopenia with platelet count < 150,000/mL - Individuals of Han Chinese or Thai descent with HLAB5801 genetic phenotype - Serious medical condition that at investigator's judgment precludes utilization of a fixed dose of allopurinol | |
| 90 | NCT02032901 | completed | 1 | phase 3 | ['hepatitis c'] | ["['B18.2', 'B17.10', 'B17.11', 'B19.20', 'B19.21', 'B15.0', 'B15.9']"] | ['daclatasvir', 'sofosbuvir'] | ['CC(C)C(C(=O)N1CCCC1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)C6CCCN6C(=O)C(C(C)C)NC(=O)OC)NC(=O)OC', 'CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3'] | For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Key Inclusion Criteria: - Subjects must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications - Subjects chronically infected with hepatitis C virus (HCV) genotype 3 - Subjects who are HCV treatment-naive - Subjects who are HCV treatment-experienced (previous exposure to non-structural 5A inhibitors is prohibited) - HCV RNA ≥10,000 IU/mL at screening Key Exclusion Criteria: - HCV Genotypes other than genotype-3 infection; mixed genotype infections are not permitted - Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair - Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening - Documented or suspected hepatocellular carcinoma, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed) - Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy | |
| 91 | NCT02035124 | withdrawn | study withdrawn due to slow accrual. no patients were enrolled. | 0 | phase 2 | ['advanced prostate cancer'] | ["['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['bkm 120', 'cabazitaxel'] | ['C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4', 'CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)OC)C)OC'] | Inclusion Criteria: 1. Adenocarcinoma of the prostate confirmed histologically. 2. Metastatic disease confirmed by biopsy or imaging studies. 3. Patients must have received treatment with docetaxel as the only previous chemotherapy regimen. In addition, previous treatment with hormonal agents and/or immune therapy is allowed (e.g., abiraterone). (Previous treatment with MDV3100 will also be allowed.) 4. Patients must be castrate-resistant (i.e. developed progression of metastases following surgical castration or during medical androgen ablation therapy) with documented castrate levels of testosterone (<50 ng/dl). 5. Patients receiving medical castration therapy with gonadotropin-releasing hormone (GnRH) analogues should continue this treatment during this study. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2. 7. Patient must have progressive metastatic prostate cancer by at least 1 of the following criteria: - Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. - Bone scan progression defined by 2 or more new lesions on bone scan. - Prostate specific antigen (PSA) progression is determined by a minimum of three rising PSA levels with an interval of ≥1 week between each determination. The screening PSA measurement (documenting progression) must be ≥2 ng/mL. 8. Screening PSA ≥2 ng/mL. 9. Adequate hematologic, renal and hepatic function: 10. Adequate serum chemistries. 11. Ability to swallow and retain oral medication. 12. Life expectancy of ≥6 months. 13. Patients must be ≥18 years of age. 14. Patients entering this study must be willing to provide tissue from a previous tumor biopsy or 15 unstained slides (if available) for correlative testing. If tissue is not available, a patient will still be eligible for enrollment into the study. 15. Ability to understand the nature of this study and give written informed consent. Exclusion Criteria: 1. Previous treatment with PI3K inhibitors. 2. Known hypersensitivity to BKM120 or polysorbate-80 or any of the excipients or taxanes. 3. Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of BKM120. For investigational drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the investigational drug and administration of BKM120 is required. 4. Previous chemotherapy with any agent other than docetaxel. All patients must be ≥28 days after their most recent chemotherapy and have recovered from side effects. 5. Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy. 6. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. 7. Clinical significant peripheral neuropathy (defined as CTCAE v4.0 Grade ≥2) regardless of causality. 8. Mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of ≥12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off score of ≥ 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score or the PHQ-9) - anxiety or depression ≥ Grade 3 - medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation, or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified 9. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 28 days (4 weeks) have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases. 10. Leptomeningeal metastases or spinal cord compression due to disease. 11. Acute or chronic liver, renal disease or pancreatitis. 12. Uncontrolled diabetes mellitus. Type II diabetics are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Type I diabetics are eligible if HbAlc is <8. 13. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome). 14. Any of the following cardiac diseases currently or within the last 6 months: - Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 480 ms on screening ECG - Unstable angina pectoris - Congestive heart failure (New York Heart Association [NYHA] ≥ Grade 2 - Acute myocardial infarction - Conduction abnormality not controlled with pacemaker or medication - Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible.) - Valvular disease with significant compromise in cardiac function. 15. Family history of congenital long or short QT, or known history of QT/QTc prolongation or Torsades de Pointes (TdP). Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or induce TdP and the treatment cannot either be discontinued or switched to a different medication prior to starting study treatment. 16. Inadequately controlled hypertension (i.e., SBP>180 mmHg or DBP>100mmHg). (Patients with values above these levels must have their BP controlled with medication prior to starting treatment) 17. Patient receiving chronic treatment with systemic steroids or another immunosuppressive agent at the start of study treatment. Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. 18. Patients receiving drugs known to be moderate and strong inhibitors or inducers or isoenzyme cytochrome P450 (CYP) 3A (CYP3A) that cannot be discontinued or switched to different medication prior to starting study drug. 19. Patients who have taken herbal medications and certain fruits ≤7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits. 20. Patients currently receiving treatment with therapeutic doses of warfarin sodium. Patients receiving low molecular weight heparin are allowed. 21. A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 22. Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV). 23. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer. 24. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 25. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol. 26. Fertile male patients, defined as all males physiologically capable of conceiving offspring must use a highly effective contraception during dosing any study agent + [5 x T1/2] +12 weeks = contraception through 16 weeks after final dosing of study therapy and should not father a child during this period. In addition, female partners of male patients must use a highly effective contraception during dosing of any study agent + [5 x T1/2] +12 weeks = contraception through 16 weeks after the final dose of study therapy. |
| 92 | NCT02030600 | completed | 1 | phase 3 | ['diabetes', 'diabetes mellitus, type 2'] | ["['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']", "['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['insulin degludec', 'insulin glargine'] | ['CCC(C)C1C(=O)NC2CSSCC(C(=O)NC(CSSCC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)NC(CC(=O)N)C(=O)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC7=CC=C(C=C7)O)C(=O)NC(C(C)O)C(=O)N8CCCC8C(=O)NC(CCCCNC(=O)CCC(C(=O)O)NC(=O)CCCCCCCCCCCCCCC(=O)O)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)C(CC(C)C)NC(=O)C(CC2=CNC=N2)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC2=CC=CC=C2)N)C(=O)NC(C(=O)NC(C(=O)N1)CO)C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C(C)CC)NC(=O)CN', 'CCC(C)C1C(=O)NC2CSSCC(C(=O)NC(CSSCC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)NCC(=O)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC7=CC=C(C=C7)O)C(=O)NC(C(C)O)C(=O)N8CCCC8C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCNC(=N)N)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)C(CC(C)C)NC(=O)C(CC2=CNC=N2)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC2=CC=CC=C2)N)C(=O)NC(C(=O)NC(C(=O)N1)CO)C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C(C)CC)NC(=O)CN'] | Inclusion Criteria: - Male or female, age at least 18 years at the time of signing informed consent - Subjects fulfilling at least one of the below criteria: a) Experienced at least one severe hypoglycaemic episode within last year (according to the ADA (American Diabetes Association) definition, April 2013), b) Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m^2 per CKD-Epi (Chronic Kidney Disease Epidemiology Collaboration) by central laboratory analysis, c) Hypoglycaemic symptom unawareness, d) Exposed to insulin for more than 5 years, e) Recent episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (below or equal to 70 mg/dL [below or equal to 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening) - Type 2 diabetes mellitus (diagnosed clinically) for at least 26 weeks prior to Visit 1 - Current treatment with any basal insulin (OD or BID) ± any combination of OADs (metformin, DPP-4 inhibitor, alpha-glucosidase inhibitor, thiazolidinediones, and SGLT2-inhibitor) for 26 weeks or longer prior to Visit 1 For subjects on BID the total daily dose should be below 75 units - HbA1c (glycosylated haemoglobin) below or equal to 9.5 % by central laboratory analysis - BMI (body mass index) below or equal to 45 kg/m^2 Exclusion Criteria: - Treatment with a bolus insulin separately or contained in an insulin mix product within the last 26 weeks prior to Visit 1 - Use of any other anti-diabetic agent(s) than those stated in the inclusion criteria within the last 26 weeks prior to Visit 1 | |
| 93 | NCT02036515 | completed | 1 | phase 3 | ['type 2 diabetes mellitus'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['ertugliflozin 5 mg', 'ertugliflozin 15 mg', 'placebo for ertugliflozin 5 mg', 'metformin', 'sitagliptin', 'glimepiride', 'placebo for ertugliflozin 10 mg'] | ['CN(C)C(=N)N=C(N)N', 'C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)CC(CC3=CC(=C(C=C3F)F)F)N', 'CCC1=C(CN(C1=O)C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC3CCC(CC3)C)C'] | Inclusion Criteria: - Diagnosis of type 2 diabetes mellitus (T2DM) - On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin - Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2 - Male, postmenopausal female or surgically sterile female - If a female of reproductive potential, agrees to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug Exclusion Criteria: - History of type 1 diabetes mellitus or a history of ketoacidosis - History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug- or chemical-induced, and post-organ transplant) - A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) or DPP-4 inhibitor - On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable - Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable - Has been treated with insulin (except for short-term use [<= 7 days]), injectable antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2) inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™), colesevelam (Welchol™), or any other non-protocol approved AHAs within 12 weeks of study participation - Has active, obstructive uropathy or indwelling urinary catheter - History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation - A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer - Known history of Human Immunodeficiency Virus (HIV) - Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) - A medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease - Has any clinically significant malabsorption condition - If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation - Has been previously randomized in a study with ertugliflozin - Has participated in other studies involving an investigational drug within 30 days prior or during study participation - Has undergone a surgical procedure within 6 weeks prior to or planned major surgery during study participation - Has a positive urine pregnancy test - Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication - Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication - Excessive consumption of alcoholic beverages or binge drinking - Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial | |
| 94 | NCT02032888 | completed | 1 | phase 3 | ['hepatitis c'] | ["['B18.2', 'B17.10', 'B17.11', 'B19.20', 'B19.21', 'B15.0', 'B15.9']"] | ['daclatasvir', 'sofosbuvir'] | ['CC(C)C(C(=O)N1CCCC1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)C6CCCN6C(=O)C(C(C)C)NC(=O)OC)NC(=O)OC', 'CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3'] | For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Key Inclusion Criteria: - Patients must be able to understand and agree to/comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications - Patients chronically infected with hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6, as documented by positive HCV RNA at screening - Patients who are HCV treatment-naive - Patients who are HCV treatment-experienced and who have had prior anti-HCV therapies discontinued or completed at least 12 weeks prior to screening - Patients with HCV RNA ≥10,000 IU/mL at screening - Patients with HIV-1 infection Key Exclusion Criteria: - Presence of AIDs-defining opportunistic infections, as defined by the Centers of Disease Control and Prevention, within 12 weeks prior to study entry - Patients infected with HIV-2 - Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair - Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening - Documented or suspected hepatocellular carcinoma, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed - Evidence of decompensated liver disease, including radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy | |
| 95 | NCT02036476 | terminated | lack of accrual. | 0 | phase 2 | ['merkel cell carcinoma', 'skin cancer'] | ["['C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8', 'Z85.821']", "['C79.2', 'C44.500', 'C44.90', 'D23.9', 'D48.5', 'C44.00', 'C44.301']"] | ['cabozantinib'] | ['COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F'] | Inclusion Criteria: - Must have histologically or cytologically confirmed Merkel Cell Carcinoma that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan (see section 10 for the evaluation of measureable disease). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented - Must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. Patients are also eligible if they received curative intent platinum-based therapy and progressed within a year of therapy - No prior MET inhibitor is allowed - At least 2 weeks since prior chemotherapy or radiation therapy. At least 3 weeks since prior biologics or investigational agents - Recovery from effects of recent treatment to baseline or CTCAE ≤ grade 1 toxicity from all prior therapies except alopecia and other non-clinically significant AEs - Participants must be ≥18 years of age - ECOG performance status ≤1 - Participants must have normal organ and marrow function - Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation - Ability to understand and the willingness to sign a written informed consent document - Collection of archival tissue specimens for confirmation of Merkel Cell Carcinoma Exclusion Criteria: - Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier - Participants may not be receiving any biologics or investigational agents within 3 weeks - The subject has active brain metastases or epidural disease - History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib - Has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 the institutional ULN within 7 days before the first dose of study treatment, unless PT/PTT prolongation known to be secondary to conditions not associated with increased bleeding risk (as on antiphospholipid antibody syndrome) - Requires concomitant treatment, in therapeutic doses, with anticoagulants - Active bleeding or pathologic conditions that carry high risk of bleeding - Have experienced clinically significant gastrointestinal bleeding within 6 months before first dose of study treatment - Requires chronic concomitant treatment of strong CYP3A4 inducers - Is unable or unwilling to swallow tablets - Has a corrected QT interval calculated by the Fridericia formula (QTcF)>500 ms within 28 days before initiation of cabozantinib - Has evidence of tumor invading the GI tract or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib - Has radiographic evidence of cavitating pulmonary lesion(s) - Has uncontrolled, significant intercurrent or recent illness - Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy - History of major surgery within 3 months or minor surgery within 1 month of the first dose of cabozantinib - Pregnant women - Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy - HIV-positive individuals on combination antiretroviral therapy |
| 96 | NCT02031536 | terminated | slow accrual | 0 | phase 2 | ['gastrinoma', 'glucagonoma', 'insulinoma', 'liver metastases', 'pancreatic polypeptide tumor', 'recurrent islet cell carcinoma', 'somatostatinoma'] | ["['Z52.6', 'K71.8', 'K71.7', 'A06.4', 'C22.0', 'C22.3', 'K70.0']", "['K90.3', 'K86.81', 'Q45.2', 'C25.3', 'E16.9', 'E16.8', 'Q45.3']", "['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['everolimus'] | ['CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OCCO)C)C)O)OC)C)C)C)OC'] | INCLUSION CRITERIA: - Patients must have histologically or pathologically confirmed metastatic low or intermediate grade pancreatic neuroendocrine tumor(s) to the liver as per the Klimstra guidelines - Patients must have recovered from an R0 or R1 resection of all disease (including resection of a primary primitive neuroectodermal tumor [PNET] if present); patients may have had resection plus microwave or radiofrequency ablation, provided that no ablated lesion was >= 5 cm prior to ablation - Patients must be within 4 to 8 weeks from the completion of surgery at time of randomization - Patients must have paraffin-embedded fixed metastatic tumor tissue available for submission for central review; core biopsy or surgical specimens required - Patients must have post-operative computed tomography (CT) or magnetic resonance imaging (MRI) prior to randomization and =< 4 weeks after completion of surgery to confirm disease status; patients must be able to tolerate CT or MRI imaging including contrast agents as required for the protocol - Women of child-bearing potential and sexually active males must be strongly advised to use an accepted and highly effective method of contraception or abstain from sexual intercourse for the duration of their treatment through 8 weeks after their last dose of protocol therapy; women of child-bearing potential, sexually active males, and the female partners of male participants should be advised of the risk of becoming pregnant or fathering a child while receiving protocol treatment; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately - Prior treatment with sunitinib and/or cytotoxic chemotherapy are allowed provided last dose was > 30 days prior to randomization - Prior chemoembolization is allowed provided last dose was > 30 days prior to randomization - Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X institutional ULN - Serum creatinine =< 1.5 X institutional ULN or creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 X institutional normal - Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN - Absolute neutrophil count >= 1,500/mm^3 - Leukocytes >= 3,000/mm^3 - Platelets >= 100,000/mm^3 - Hemoglobin >= 9 g/dL - Patients with a history of the following within =< 12 months of randomization are not eligible - Arterial thromboembolic events - Unstable angina - Myocardial infarction - Patients with known history of abnormal pulmonary function must have documentation of diffusing capacity of the lung for carbon monoxide (DLCO) of > 50% predicted and oxygen saturation (SaO2) of > 87% at rest on room air =< 4 weeks prior to randomization - Patients with unexplained pulmonary infiltrates must have pulmonary function tests within the institutional limits of normal =< 4 weeks prior to randomization - Patients with poorly controlled diabetes mellitus as defined by hemoglobin A1c (HbA1c) > 8% despite adequate therapy are ineligible; patients with a known history of impaired fasting glucose or diabetes mellitus must have blood glucose and antidiabetic treatment monitored closely throughout the trial and adjusted as necessary - Patients may not be receiving any other investigational agents while on study treatment; prior treatment with other investigational agent is allowed provided last dose was >= 30 days prior to randomization - Patients must NOT have received live attenuated vaccines =< 1 week prior to randomization; patients should also be advised not to receive live attenuated vaccines during the study and to avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 - Patients must have life expectancy >= 12 weeks - Patients should be advised to avoid drugs or foods that are known potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers EXCLUSION CRITERIA: - Patients have received prior everolimus - Patients have either clinically apparent central nervous system metastases or carcinomatous meningitis =< 6 months prior to randomization - Women are pregnant or breast-feeding; all females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy - Patients are on chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed - Patients have history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus - Patients have known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) - Patients have absorption issues that would limit the ability to absorb everolimus - Patients have a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study - Patients have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions: - Non-melanoma skin cancer, in situ cervical cancer, breast cancer in situ, or superficial bladder cancer (noninvasive papillary carcinoma or carcinoma in situ); OR - Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years - Patients have severe and/or uncontrolled medical conditions such as: - Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to randomization, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease - Symptomatic congestive heart failure of New York Heart Association class III or IV - Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA]) - Active, bleeding diathesis - Patients have known history of human immunodeficiency virus (HIV) seropositivity - Patients have experienced thrombotic events (deep vein thrombosis, pulmonary embolism) =< 3 months prior to randomization - Patients have liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis at randomization; patients at increased risk for hepatitis B or hepatitis C must be screened for hepatitis prior to randomization - Patients have ongoing cardiac dysrhythmia of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) grade >= 2, uncontrolled atrial fibrillation of any grade, or corrected QT (QTc) interval > 470 msec - Patients have history of severely impaired pulmonary function for their age |
| 97 | NCT02038816 | terminated | accrual too slow, insufficient patients | 0 | phase 2 | ['myelodysplastic syndromes'] | ["['D46.9', 'D46.C', 'D46.Z']"] | ['deferasirox + azacitidine', 'azacitidine'] | ['C1=NC(=NC(=O)N1C2C(C(C(O2)CO)O)O)N'] | Inclusion Criteria: - Adults >18 yrs of age - WHO defined MDS with Higher risk MDS (IPSS int-2/high) - Azacitidine X at least 6 cycles with no hematologic improvement/no disease progression as per IWG 2006 criteria - Ferritin >500 µg/L - If transfusion independent, must have Hb <110 g/L OR Neutrophils < 1,000/mL OR Platelets < 100,000/mL - ECOG ≤2 - CrCl >40 ml/min Exclusion Criteria: - Increased ALT (>300 U/L) - Uncontrolled infection - HIV+ - Pregnant or breast-feeding - Previous and concurrent iron chelation - Concurrent use of hematopoietic growth factors including erythropoietin, darbepoietin and granulocyte colony stimulating factor - Concurrent use of other disease modifying agents including cytotoxic chemotherapy, histone deacetylase inhibitors, other hypomethylating agents or lenalidomide |
| 98 | NCT02382406 | terminated | the study was completed. it was fully accrued. | 0 | phase 1/phase 2 | ['non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['carboplatin', 'nab-paclitaxel', 'mk-3475 (phase i)', 'mk-3475 (phase ii)'] | ['C1CC(C1)(C(=O)O)C(=O)O.[NH2-].[NH2-].[Pt+2]', 'CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(C5=CC=CC=C5)NC(=O)C6=CC=CC=C6)O)O)OC(=O)C7=CC=CC=C7)(CO4)OC(=O)C)O)C)OC(=O)C'] | Inclusion Criteria: - Subjects must be willing and able to provide written informed consent for the trial and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. - Subjects must be ≥ 18 years of age. - Individuals with stage IIIB or IV, unresectable non-small cell lung cancer (NSCLC) who have not received prior chemotherapy for Stage IIIB or IV disease, and who are not candidates for curative surgery or radiation therapy. - ECOG performance status (PS) 0-1 - Measurable disease by RECIST v1.1 criteria - Prior to registration, all subjects must have archival tissue available. For subjects who have no archival tissue, but have PD-L1 testing results using the Dako 22C3 antibody, subjects will be permitted to enroll without submitting tissue. If the patient has not had prior testing and no acceptable archival tissue is available, subjects must be willing to consent to providing a pre-treatment biopsy for PD-L1 testing. Regardless of PD-L1 testing status, archival tissue will be requested for research testing if available. - Phase II subjects must be willing to consent to providing a mandatory post-treatment core biopsy for research if clinical feasible. - Women are eligible to participate if they are of non-childbearing potential or have documentation of a negative pregnancy test (serum or urine β-hCG) within 3 days of registration. Sexually active pre-menopausal women of childbearing potential must agree to use adequate, highly effective contraceptive measures, starting with the first dose of study drug and for 120 days after the last dose of last study drug. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable, or injectable contraceptives plus one barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥ 1 year. - Male participants should agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of last study drug. Exclusion Criteria: - Individuals with the presence of symptomatic CNS metastases requiring radiation treatment, surgery, or ongoing use of corticosteroids. - Untreated or brain metastasis causing any symptoms, such as neurologic deficits or headache. Individuals with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline and whole brain radiation or stereotactic radiosurgery completed over 4 weeks prior to registration), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment. - History of solid organ or stem cell transplant requiring immunosuppressive medications. - Any prior adjuvant cytotoxic chemotherapy within 12 months of registration. Subjects who received chemotherapy for earlier stage disease more than 12 months prior to study registration are eligible for this trial. - Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). - Any radiotherapy within 2 weeks prior to registration (4 weeks for brain radiotherapy as noted above). - Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. - History of other invasive malignancy that is currently active and/or has been treated within 12 months of registration. (Notable exceptions include: basal cell carcinoma, squamous cell carcinoma of the skin, localized prostate cancer, in situ carcinomas of the cervix and breast, and superficial bladder cancers [non-muscle-invasive]). - Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). - Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. - Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis. - Has a history of pneumonitis that required steroids or current pneumonitis. - Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v 4.0 criteria. - Known significant liver disease including viral, alcoholic, active hepatitis B or C, and/or cirrhosis. - Abnormal liver or renal function as defined as: bilirubin ≥ 1.5 mg/dL; AST or ALT ≥ 2.5 x the ULN; alkaline phosphatase > 2.5 x the ULN, there is no upper limit if bone metastasis is present in the absence of liver metastasis; creatinine > 1.5 mg/dL - Abnormal baseline hematologic or coagulation parameters as defined as: absolute neutrophil count (ANC) <1.5 x 10^9/L; hemoglobin < 9.0 g/dL; platelets < 100 x 10^9/L; International Normalized Ratio (INR) of prothrombin time (PT) ≥ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) ≥ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants - Has received a live vaccine within 30 days prior to the first dose of study drug. - Known activating EGFR mutation or ALK translocation - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of pembrolizumab. |
| 99 | NCT02382016 | completed | 1 | phase 4 | ['portopulmonary hypertension'] | ["['I15.0', 'I97.3', 'K76.6', 'P29.2', 'G93.2', 'H40.053', 'I10']"] | ['macitentan'] | ['CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br'] | Main Inclusion Criteria: - Male or female of at least 18 years of age - Confirmed diagnosis of portopulmonary hypertension Main Exclusion Criteria: - Severe hepatic impairment - Severe obstructive or restrictive lung disease - Pulmonary veno-occlusive disease - Systolic blood pressure (SBP) < 90 mmHg at Screening - ALT/AST >= 3 x ULN - Bilirubin >= 3 mg/dL at Screening - Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results | |
| 100 | NCT02383966 | completed | 1 | phase 3 | ['carcinoma, squamous cell of head and neck'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['cetuximab', 'cisplatin/carboplatin', '5-fluorouracil'] | ['Status: 400', 'C1=C(C(=O)NC(=O)N1)F'] | Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of SCCHN - Recurrent and/or metastatic SCCHN, not suitable for local-regional treatment - Presence of at least 1 measurable lesion according to RECIST Version 1.1 - Signed written informed consent before any trial-related activities are carried out - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Other protocol-defined inclusion criteria could apply Exclusion Criteria: - Prior systemic chemotherapy, except if given as part of multimodal treatment for locally advanced disease, that was completed within 6 months before randomization - Surgery (excluding prior biopsy for diagnosis) or irradiation within 4 weeks before trial entry - Previous treatment with monoclonal antibody or signal transduction inhibitors targeting epidermal growth factor receptor - Nasopharyngeal carcinoma - Known central nervous system metastasis and/or leptomeningeal disease - Medical or psychological condition that would not permit the participant to complete the trial or sign informed consent - Legal incapacity or limited legal capacity - Other protocol-defined exclusion criteria could apply |