Participants may not have any of the following cardiac criteria:\r\n* Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs) using the screening clinic ECG machine-derived QTc value\r\n* No history of QT prolongation associated with other medications that required discontinuation of that medication\r\n* Patient must not be receiving any concomitant medications that are known to be associated with Torsades de Pointes\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval\r\n* Symptomatic heart failure – New York Heart Association (NYHA) grade II-IV
Any of the following cardiac criteria:\r\n* Resting corrected QT interval (QTc) > 480 msec obtained from electrocardiogram (ECG)\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) eg, complete left bundle branch block, third degree heart block\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval\r\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade >= 2\r\n* Uncontrolled hypotension – systolic blood pressure (BP) < 90 mmHg and/or diastolic BP < 50 mmHg\r\n* Left ventricular ejection fraction (LVEF) below lower limit of normal for site
Patients with QTc interval > 450 msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (ex. heart failure, clinically significant hypokalemia, clinically significant hypomagnesemia, family history of long QT syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded
Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval that a patient is unable to stop
Subjects with corrected QT using Fridericia's formula (QTcF) interval of >= 450 msec if male and >= 470 msec if female; other factors that increase the risk of QT prolongation or arrhythmic events (e.g. heart failure, chronic hypokalemia, family history of long QT interval syndrome) at screening; subjects with bundle branch block should be reviewed by the principal investigator for potential inclusion
Significant medical history or unstable medical comorbidities, including:\r\n* Heart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST elevation myocardial infarction [NSTEMI] or ST elevation myocardial infarction [STEMI]) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of > 150 mm Hg or diastolic blood pressure of > 100 mm Hg while on antihypertensive medication\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 msec, mean resting corrected QT value (QTc) of > 470 msec\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval that a patient is unable to stop\r\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\r\n* Active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol\r\n* Active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV); screening for chronic conditions is not required; HIV-positive participants on combination antiretroviral therapy are ineligible
Patients with QTc interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded
QTc prolongation >450 ms or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval)
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
Any factors that increase the risk of QTc prolongation or risk of rrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
Medications with a known risk of prolongation of QT interval
No congenital long QT syndrome or known 1st degree relative with unexplained sudden death under 40 years of age
Corrected QT (QTc) interval (i.e., Friderica’s correction [QTcF]) >= 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
Any of the following cardiac abnormalities or history:\r\n* Mean resting corrected QT interval (QTc) > 470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
Any of the following cardiac criteria: \r\n* Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec;\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250msec;\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
QTc interval using Fridericia's formula (QTcF) ?450 msec or other factors that increase the risk of QT interval prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Bundle branch block and prolonged QTc are permitted with approval of the study Sponsor
Patients with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) that meets New York Heart Association (NYHA) class II or above
Positive risk assessment for cardiovascular disease including prior anthracycline cumulative dose more than 50% above recommended non-cardiotoxic levels, left ventricular ejection fraction (LVEF) <50%, valvular heart disease, or severe hypertension, (see Table 1). Cardiac subjects with a New York Heart Association (NYHA) classification of 3 or 4 will be excluded. (Cardiology consultation should be requested if any question arises about cardiac function.) This also includes subjects with baseline QT/QTc interval >480 msec, a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and using concomitant medications that significantly prolong the QT/QTc interval.
Has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT. syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age
History of risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome); concomitant use of medications with a low risk of QT/QTc prolongation (including, but not limited to diphenhydramine, famotidine, ondansetron) is permissible
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
QT prolongation and/or familiar history of QT prolongation and uncontrolled cardiac arrhythmias
Any of the following cardiac criteria\r\n* Resting corrected QT interval (QTc using Fridericia’s formula) > 480 msec\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograph (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval \r\n** Symptomatic congestive heart failure or left ventricular ejection fraction (LVEF) < 50%
known and possible risk for QT prolongation
Mean corrected QT interval (QTc) > 480 msec or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in a next-of-kin relative.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
History of QT prolongation associated with other medications that required discontinuation of that medication
Any of the following cardiac criteria:\r\n* Mean resting corrected QT interval (Fridericia's correction formula [QTcF]) > 470 ms ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
Any factor increasing the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QT interval.
Any of the following cardiac criteria: Mean resting QT interval corrected for heart rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); performed within 28 days prior to sub-study registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); patients must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age
Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); performed within 28 days prior to Step 2 re-registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); patients must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age
Subjects with heart-rate corrected QT (QTc) interval ?450 ms or other factors that increase the risk of QT prolongation or arrhythmic events.
Patients with QTc interval ?450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
Clinically significant ECG abnormalities or any factors that increase the risk of corrected QT interval prolongation or risk of arrhythmic events
Concomitant medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age)
Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital or familial long QT syndrome or family history of unexplained sudden death under 40 years of age or any concomitant medications known to prolong QT interval.
Subjects with heart-rate corrected QT (QTc) interval ? 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval.
Subjects with heart-rate corrected QT (QTc) interval ?450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening.
No clinical evidence of heart failure or history of untreated ejection fraction below the lower limit of normal per institutional standards, or significant QT prolongation (> grade 1, 480 msec) no history of congenital long QT syndrome, and no use of drugs known to increase the risk of torsades de point - patients may be eligible for study if the drug can be changed to another agent with less risk
QT related exclusion criteria:\r\n* QT interval corrected using Fridericia’s formula (QTcF) at screening > 470 msec\r\n* History of syncope or family history of idiopathic sudden death\r\n* Sustained or clinically significant cardiac arrhythmias\r\n* Risk factors for torsades de pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block\r\n* Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism or cardiac failure\r\n* Concomitant medication(s) known to increase the QT interval
Impaired cardiac function including ongoing cardiac dysrhythmias of grade > 2, ejection fraction < 50%, atrial fibrillation of any grade, or corrected QT (QTc) prolongation > 450 ms, or other factors that increase the risk of QT prolongation (i.e. family history of long QT interval syndrome, hypokalemia defined as serum potassium < 3.0 mEq/L)
Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
Heart-rate corrected QT (QTc) interval >450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion
Patients with a corrected QT interval (QTc) at baseline of > 450 milliseconds or other factors that increase the risk of QT prolongation or arrhythmic events (i.e., heart failure, hypokalemia with potassium < 3.5 despite supplementation, family history of long QT syndrome) should be excluded
Known history of QT prolongation or is taking any medication known to lead to QT prolongation
Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
Cardiovascular disease, including recent history of or currently clinically symptomatic and uncontrolled congestive heart failure, arrhythmia, angina, corrected QT (QTc) prolongation or other QTc risk factors, myocardial infarction; patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age;
Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
Has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation
Has any factors that increase the risk of corrected QT (QTc) interval prolongation or risk of arrhythmic events, such as congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
Concomitant medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age)