A history of any of the following: sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy
Have documented major electrocardiogram (ECG) abnormalities which are clinically significant at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle-branch blocks, ventricular hypertrophy, or recent myocardial infarction).
History or family history of Long QT Syndrome or Torsade de Pointes. Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within  months or greater than Class  Angina Pectoris or NYHA Heart Failure Class >. QTcF >  msec, PR >  msec, Mobitz II nd degree AV Block, : AV Block, High Grade AV Block, or Complete Heart Block, unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities.
Known history of symptomatic congestive heart failure (New York Heart Association III-IV), symptomatic or poorly controlled cardiac arrhythmia, complete left bundle branch block, bifascicular block, or any clinically significant ST segment and/or T-wave abnormalities, QTcF >  msec prior to randomization.
AZD plus olaparib\r\n* Patients with breast, ovarian and endometrial cancers that carry an AKT mutation are excluded from the study due to another ongoing study that enrolls these patients; patients with these tumor types but other mutations can be enrolled in the study\r\n* Patients with type I or type II diabetes mellitus; type II diabetes mellitus is allowed if well controlled by dietary measures alone with a glycated hemoglobin (HbgAc) < %; patients found to have a fasting glucose >=  mmol/L ( mg/dL) or HbgAc > % ( mmol/L) at screening should be assessed for appropriate management according to local policy, of which those in whom dietary measures alone provide good diabetic control (HbgAc < %) will be eligible for inclusion\r\n* Patient must have no evidence of troponin elevation (any common toxicity criteria [CTC] grade)\r\n* Patient must not have > stage II New York Heart Association (NYHA) classification cardiac status; recent history (i.e., within  months) of coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infarction [MI])\r\n* Patient must not have resting left ventricular ejection fraction (LVEF) < % measured by multi-gated acquisition (MUGA)/echocardiogram (ECHO)\r\n* Patient must not have PR interval greater than  msec\r\n* Patient must not have clinically significant PR (PQ) interval prolongation\r\n* Patient must not have resting LVEF < % measured by echocardiogram, regional wall abnormality on ECHO, or any clinically significant structural abnormalities on echocardiogram such as left ventricular hypertrophy or diastolic dysfunction or valvular disease\r\n* Patient must not have QTcF >  msec or b) family history of long QT Syndrome or\r\nc) evidence of recent myocardial infarction e.g. within  months prior to start of study treatment) or risk of having a re-infarction, or d) history of torsade de pointes or e) QTcF <  msec (short QT syndrome)\r\n* Patient must not have intermittent second or third degree atrioventricular (AV) block (second degree AV block [Mobitz Type I and II]; third degree AV block [complete heart block]); incomplete, full or intermittent bundle branch block (QRS -ms with normal QRS and T wave morphology is permitted if there is no evidence of left ventricular hypertrophy); Mobitz type , Wenckebach while asleep is permitted\r\n* Patient must not have clinically significant abnormalities in T wave or ST-T changes that can be indicative or be suggestive of acute ischemic changes or acute injury pattern\r\n* Use of any known potent negative inotropic drug - calcium channel blockers: verapamil, diltiazem; beta-blockers (pending discussion with cardiac SKG): metoprolol, propranolol, atenolol, bisoprolol, carvedilol, timolol, sotalol, esmolol; anti- arrhythmics (class I): disopyramide, procainamide, mexiletine; (class III): amiodarone\r\n* Patients with uncontrolled hypotension (systolic blood pressure <  mmHg and/or diastolic blood pressure <  mmHg)\r\n* Patients with potassium or sodium levels outside the normal range for the site\r\n* Patients with proteinuria (+ on dipstick analysis or >  mg/ hours)
For Part G: Have a baseline electrocardiogram (obtained from Day - to Day -) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB ? milliseconds).
Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block  and , sino-atrial block)
Pathologic bradycardia or heart block
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction Exclusions Related to Infections
Electrocardiogram (ECG) abnormalities:\r\n* Prolonged corrected QT (QTc) (Bazettes or Fredericias correction) interval on screening ECG (>=  msec)\r\n* QRS ?  msec\r\n* PR ?  msec\r\n* Any prior history, or current evidence of second- or third-degree heart block\r\n* Heart rate ?  beats per minute at screening\r\n* ECG second degree heart block (Mobitzs type  or Wenckebach)\r\n* Complete heart block\r\n* Left bundle branch block or bifascicular block (right bundle branch block and left anterior hemiblock together)\r\n* Episodes of ventricular tachycardia
Subjects with a history of significant cardiac disease including: congestive heart failure requiring therapy; history of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within  months prior to starting study treatment; clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block); left ventricular ejection fraction (LVEF) < % evaluated by echocardiogram (ECHO) or multigated acquisition scan (MUGA); increased Fridericia's correction formula (QTcF) (>  for men and >  for women).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (New York Heart Association [NYHA] class >=  or left ventricular ejection fraction < %), unstable angina pectoris, myocardial infarction within the last  months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] permissible), or psychiatric illness/social situations that would limit compliance with study requirements
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmics are excluded; recent onset atrial fibrillation not in sinus rhythm and without cardiology evaluation are excluded; st degree AV block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are not excluded), or\r\n* Congestive heart failure (chf) of New York Heart Association (NYHA) class >= , or\r\n* myocardial infarction (mi) within  months
Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block).
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block/right bundle branch block [LAFB/RBBB] will not be excluded), or \r\n* Congestive heart failure (CHF) New York Heart Association (NYHA) class >= , or \r\n* Myocardial infarction (MI) within  months\r\n* Left ventricular ejection fraction <  %\r\n* Hypertension >  mm Hg systolic or >  mm Hg diastolic with or without antihypertensive therapy
uncontrolled or clinically significant conduction abnormalities; first degree AV block or asymptomatic LAFB/RBBB are eligible
Unstable cardiovascular function: symptomatic ischemia, or uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or congestive heart failure (CHF) New York Heart Association (NYHA) class , or myocardial infarction (MI) within  months; left ventricular ejection fraction < %; hypertension >  millimeter of mercury (mm Hg) systolic or >  mm Hg diastolic with or without antihypertensive therapy
Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmic agents are excluded; st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded); or
Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding  months, and significant conduction abnormalities, including but not limited to nd degree atrioventricular block (AV block) type II, rd degree block, QT prolongation (corrected QT [QTc] >  millisecond [msec]), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate <  beats per minute [bpm]), hypotension, light headedness and syncope; patients with persistent and uncontrolled atrial fibrillation will be excluded; the protocol excludes patients who have recently had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin or equivalent vitamin K antagonist
History of significant cardiac disease defined as:\r\n* Symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] classes III-IV)\r\n* High-risk uncontrolled arrhythmias; i.e. atrial tachycardia with a heart rate > /min at rest, significant ventricular arrhythmia or higher-grade atrioventricular (AV) block (second degree AV-block type  [mobitz ] or third degree AV-block)\r\n* Prolongation of QT interval >  msecs\r\n* History of myocardial infarction within last  months\r\n* Clinically significant valvular heart disease\r\n* Angina pectoris requiring anti-angina treatment\r\n* Current uncontrolled hypertension (persistent systolic >  mmHg and/or diastolic >  mmHg); initiation or adjustment of anti-hypertensive medication is permitted prior to study entry
Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (i.e.: ventricular tachycardia on antiarrhythmics are excluded and first [st] degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), congestive heart failure (CHF) of New York Heart Association (NYHA) class >= , or myocardial infarction (MI) within  months
Impaired cardiac function including any of the following: Screening ECG with a QTc > msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF) at Screening and on Day  prior to the first dose of AC. The QTcF will be derived from the average QTcF in triplicate.; If QTcF> msec on Day , AC will not be given; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia requiring medical intervention; Any history of clinically significant ventricular fibrillation or torsades de pointes; Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker); Sustained heart rate of </minute on pre-entry ECG; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina within  months prior to starting study drug; CHF NY Heart Association class III or IV.
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
Any other clinically significant heart disease, including angina pectoris, resting bradycardia, left bundle branch block, ventricular tachyarrhythmia, unstable atrial fibrillation, acute myocardial infarction, or heart disease requiring cardiac pacemaker or implantable cardioverter/defibrillator
Cardiac disease that would preclude the use of any of the drugs included in the GI treatment regimen; this includes but is not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome\r\n* Corrected QT (QTc) >= ms
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block/right bundle branch block [left anterior fascicular block (LAFB)/right bundle branch block (RBBB)] will not be excluded), or\r\n* Congestive heart failure (CHF) New York Heart Association (NYHA) class >= , or\r\n* Myocardial infarction (MI) within  months
Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block
Clinically significant cardiovascular disease (that is, active or < months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ? II), second-degree or third-degree AV block (unless paced) or any AV block with PR > msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ?, uncontrolled atrial fibrillation of any grade, bradycardia defined as < bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc > msec, or congenital long QT syndrome.
Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmics are excluded, st degree AV block or asymptomatic LAFB/RBBB are eligible)
History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<  bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Patients with a history of atrial arrhythmias should be discussed with the Medical Monitor.
History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<  bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Subjects with a history of atrial arrhythmias should be discussed with the medical monitor
Abnormal ECGs that are clinically significant such as QT prolongation (QTc >  msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block or existing left bundle branch block, or signs of new, active ischemia a. Patients with evidence of prior infarction who are New York Heart Association (NYHA) functional class II, III, or IV are excluded, as are patients with marked arrhythmia such as Wolff Parkinson White pattern or complete atrioventricular (AV) dissociation
Wolff-Parkinson White syndrome or first/second/third degree atrioventricular (AV) block or sinus node dysfunction or the presence of an intra-cardiac defibrillator
have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrio ventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or \r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or\r\n* Congestive heart failure (CHF) NYHA class >= , or\r\n* Myocardial infarction (MI) within  months
Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding  months, and significant conduction abnormalities, including but not limited to second (nd) degree atrioventricular (AV) block type II, third (rd) degree block, QT prolongation (corrected QT [QTc] >  msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate <  beats per minute [bpm]), hypotension, light headedness and syncope; patients with active atrial fibrillation will be excluded; the protocol excludes patients who have within the past year had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin equivalent vitamin K antagonist
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmics are excluded and st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= , or\r\n* Myocardial infarction (MI) within  months
Significant cardiac disease or risk factors as indicated by MUGA or echocardiogram performed =<  days prior to registration and/or by presence of any of the following:\r\n* History of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version .) grade >=  symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria class >= II\r\n* Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease\r\n* High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > /min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type  [Mobitz ] or third degree AV-block])\r\n* Significant symptoms (grade >= ) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia\r\n* Myocardial infarction within  months prior to randomization\r\n* Uncontrolled hypertension (systolic blood pressure >  mmHg and/or diastolic blood pressure > mmHg)\r\n* Evidence of transmural infarction on electrocardiogram (ECG)\r\n* Requirement for oxygen therapy
Major cardiac-related diseases, medications, or laboratory abnormalities including the following: a) clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker, b) ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (eg, sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted; c) use of medications that have been linked to the occurrence of torsades de pointes, d) second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker, e) complete left bundle branch block (LBBB), f) history of long QT Syndrome or a family member with this condition, g) if baseline QTc >  ms, average of triplicate electrocardiogram (ECG) recordings is necessary; if average value of QTc is >  ms, patient is ineligible for the study; h) serum potassium, magnesium, and calcium levels outside the laboratory's reference range
Any history of second- or third-degree heart block. (Patients with pacemakers may be eligible.)
Inability to determine the QTcF interval Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block).
Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding  months, and significant conduction abnormalities, including but not limited to atrial fibrillation, nd degree atrioventricular (AV) block type II, rd degree block, torsades de pointes, QT prolongation (corrected QT [QTc] >  msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate <  beats per minute [bpm]), hypotension, light headedness and syncope; patients with atrial fibrillation will be excluded even if they are rate-controlled; if there are any active cardiac issues, cardiology consultation will be obtained for clearance
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= , or\r\n* Myocardial infarction (MI) within  months of cycle  day  dose
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and first (st) degree atrioventricular (AV) block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded)\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= , or\r\n* Myocardial infarction (MI) within  months of initiation of therapy
Adequate cardiac conduction by ECG without evidence of second- or third-degree atrioventricular block and meeting all of the following ECG criteria:
Myocardial infarction within  months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including st degree atrioventricular [AV]-block, Wenckebach type nd degree heart block, or left bundle branch block; prior to study entry, any electrocardiogram [ECG] abnormality at screening has to be documented by the investigator as not medically relevant); Note: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
Serious cardiac illness, defined as follows:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permised\r\n* Use of medications that have been linked to the occurrence of torsades de pointes; investigators should note that Zofran (ondansetron) has been linked to corrected QT (QTc) prolongation and the occurrence of torsades de pointes; therefore it should not be used in patients being treated with ganetespib; the use of all other serotonin  HT antagonists is acceptable (e.g., palonosetron, granisetron, tropisetron)\r\n* Second-or third degree atrioventricular block (AV block) unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome or a family member with this condition
Severe sinus bradycardia; heart block, second or third degree or sick sinus syndrome (if no artificial pacemaker present)
Myocardial infarction within  months prior to enrollment or has New York Heart Association (NYHA) class IIIB or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including st degree atrioventricular (AV)-block, Wenckebach type nd degree heart block, or left bundle branch block; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be evaluted by the investigator or an authorized physician sub-investigator); note: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
Patients with any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within  months\r\n* Prolonged QTc >  msec by the Fridericia correction\r\n* Major conduction abnormality, such as nd or rd degree heart block or symptomatic bundle branch block, unless a cardiac pacemaker is present
Known serious cardiac illness or medical conditions, including but not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (eg, sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Use of medications that have been linked to the occurrence of torsades de pointes\r\n* Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT Syndrome or a family member with this condition\r\n* Corrected QT (QTc) >  ms (average of triplicate electrocardiogram [ECG] recordings); a consistent method of QTc calculation is recommended for each patients QTc measurements; QTcF (Fridericias formula) is preferred\r\n* Serum potassium, magnesium, and calcium levels outside the laboratorys reference range
Unstable cardiovascular function that includes and may not be limited to:\r\n* Symptomatic myocardial ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmics are excluded and first [st] degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class , or\r\n* Myocardial infarction (MI) within  months
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
Known serious cardiac illness or medical conditions, including but not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Use of medications that have been linked to the occurrence of Torsades de pointes \r\n* Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome or a family member with this condition\r\n* Corrected QT (QTc) >  ms (average of triplicate electrocardiogram [ECG] recordings); a consistent method of QTc calculation must be used for each patients QTc measurements; QTcF (Fridericias formula) is preferred\r\n* Serum potassium, magnesium, or calcium levels in the following ranges:\r\n** Potassium < . or > . mmol/L\r\n** Magnesium < . or > . mg/dL\r\n** Calcium < . or > . mg/dL
Patients with known serious cardiac illness or medical conditions, including but not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, unstable angina or history of myocardial infarct within  months prior to enrollment, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with antiarrhythmic agents\r\n* Second- or third-degree atrioventricular block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block\r\n* History of long QT syndrome or a family member with this condition
Evidence of active heart disease within the  months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction, torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia, heart block, or congenital long QT syndrome
History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< bpm), heart block (excluding st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
History of clinically significant cardiac dysfunction, including: \r\n* Unstable angina\r\n* Unstable atrial fibrillation\r\n* Symptomatic bradycardia\r\n* Indwelling temporary pacemaker\r\n* History of myocardial infarction (MI) within  months prior to first study treatment\r\n* History of symptomatic congestive heart failure (CHF) (grade >  by NCI CTCAE or class > II by New York Heart Association [NYHA] criteria)\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class a antiarrhythmic drug (e.g. quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Second or third degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome or a family member with this condition
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
Abnormal ECGs which are clinically significant such as QT prolongation (QTc >  msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block, or signs of active ischemia. Patients with evidence of prior infarction who are New York Heart Association (NYHA) functional classes II, III, or IV are excluded, as are patients with marked arrhythmias such as Wolff Parkinson White pattern or complete atrioventricular (AV) dissociation.
Any history of second or third degree heart block;
Patients with sick-sinus syndrome, sino-atrial block, third degree heart block, atrial fibrillation, and those with permanent pacemakers
Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device; significant conduction defects (i.e.: second or third degree atrio-ventricular block or sick sinus syndrome)
History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
Unstable cardiovascular function: symptomatic ischemia (chest pain of cardiac origin), or uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or congestive heart failure (CHF) of New York Heart Association (NYHA) class >= , or myocardial infarction (MI) within  months of consent date
Significant conduction defects (i.e. second or third degree atrio-ventricular block or sick sinus syndrome)
Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).