History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < LLN (lower limit of normal range)\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
Patients must not have a history of or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec. at baseline\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration\r\n* History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multi gated acquisition scan (MUGA)\r\n* Intra-cardiac defibrillator\r\n* History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
History or evidence of increased cardiovascular risk including any of the following: \r\n* Left ventricular ejection fraction (LVEF) < institutional lower limit of normal\r\n* A QT interval corrected for heart rate using the Bazett’s formula >= 480 msec\r\n* Current clinically significant uncontrolled arrhythmias\r\n** Exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* Current >= class II congestive heart failure as defined by New York Heart Association\r\n* Patients with intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
A history or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett's formula (QTc) >= 480 msec\r\n* A history or evidence of current clinically significant uncontrolled arrhythmias\r\n** Exception: subjects with atrial fibrillation controlled for > 30 days prior to study day 1\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study day 1\r\n* A history or evidence of current >= class I congestive heart failure as defined by the New York Heart Association (NYHA) guidelines\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases
History or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec on screening electrocardiography (ECG)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
History or evidence of cardiac risk including any of the following: history or evidence of current clinically significant uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia; history of acute coronary syndromes within 6 months prior to the first dose of study therapy (including myocardial infarction and unstable angina, coronary angioplasty, or stenting); history of uncontrolled hypertension; or any history of congestive heart failure with most recent ejection fraction < 45% (screening left ventricular ejection fraction [LVEF] assessment without history of congestive heart failure CHF is not required)
Cardiac abnormalities as evidenced by any of the following: History or current clinically significant uncontrolled arrhythmias or hypertension; Clinically significant conduction abnormalities or arrhythmias, subjects with Bundle Branch Block; Presence of cardiac pacemaker; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months.
History or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s formula Bazett's correction formula (QTcB) >= 460 msec on the pre-study baseline single 12 lead EKG.\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible).\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration.\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy. In patients with no history of hypertension and a pre-study baseline blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg, a second reading should be taken at least 1 minute later, with the two readings averaged to obtain a final blood pressure (BP) measurement.\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.\r\n* Prior placement of an implantable defibrillator.\r\n* History of or identification on screening imaging of intracardiac metastases.
History or evidence of cardiovascular risk including any of the following:\r\n* LVEF< LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec;\r\n* History or evidence of current clinically significant uncontrolled arrhythmias\r\n* Clarification: Subjects with atrial fibrillation controlled (defined as not requiring change in cardiac drug dosing, emergency room visit, or hospital admission) for > 30 days prior to dosing are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study enrollment\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy;\r\n* Patients with intra-cardiac defibrillators
Any of the following cardiac abnormalities or history: a) clinically significant abnormal 12-lead electrocardiogram (ECG), QT interval (QT corrected by Bazett's formula [QTCB]) > 480 ms, b) inability to measure QT interval on ECG, c) personal or family history of long QT syndrome, d) implantable pacemaker or implantable cardioverter defibrillator, e) resting bradycardia < 55 beats/min, f) history or evidence of current clinically significant uncontrolled arrhythmias. Exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible, g) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting, within 6 months prior to randomization, h) history or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA), i) treatment refractory hypertension defined as a blood pressure of systolic > 140 mm Hg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy, j) cardiac metastases
A history or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec;\r\n* A history or evidence of current clinically significant uncontrolled arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to alternate assignment\r\n* A history or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;\r\n* Patients with intra-cardiac defibrillators;\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to -enrollment are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases
Cardiac abnormalities as evidenced by any of the following: clinically significant uncontrolled arrhythmias or uncontrolled hypertension; history or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); history of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months; baseline Corrected QT (QTc) interval using Fridericia's formula >450 milliseconds (msec) or >480 msec in subjects with Bundle Branch Block. QTc value based on single or average of triplicate ECGs obtained over a brief recording period
Any of the following cardiac abnormalities: 1. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months prior to first dose of study drug. 2. Presence of a cardiac pacemaker, 3. Baseline Corrected QT (Fridericia's formula) interval (QTcF) >=450 millisecond (msec), 4. Uncontrolled arrhythmias. Subjects with rate-controlled atrial fibrillation for >1 month prior to first dose of study drugs may be eligible.
Patients must not have significant cardiac co-morbidity including: history of acute coronary syndromes (including myocardial infarction and unstable angina) within 12 months; coronary angioplasty or stenting within 6 months; history or evidence of current >/= class III congestive heart failure as defined by the New York Heart Association (NYHA); patients with intra-cardiac defibrillators or permanent pacemakers
History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators \r\n* Known cardiac metastases
A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months or a history or evidence of current clinically significant uncontrolled arrhythmias or intra-cardiac defibrillators or abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram; subjects with grade 1 abnormalities (i.e., mild regurgitations/stenosis) may be entered; subjects with moderate valvular thickening are not eligible; subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
History or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s correction formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to taking study drug are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to taking study drug\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by antihypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases\r\n* Subjects with abnormal left ventricular ejection fraction (< 50%) on echocardiogram or multiple-gated acquisition scan (MUGA)
History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
History or evidence of cardiovascular risk including any of the following:\r\n* An average of the three most recent QT intervals corrected for heart rate using the Bazett’s formula QTcB >= 460 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* Prior placement of an implantable defibrillator\r\n* History of or identification on screening imaging of intracardiac metastases
History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricle ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to enrollment are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases\r\n* Patients with intra-cardiac defibrillators
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec at baseline \r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration\r\n* History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)\r\n* Intra-cardiac defibrillator\r\n* History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
History or evidence of cardiovascular (CV) risk including any of the following: a) Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment. c) Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association (NYHA) functional classification system. d) Recent (within the past 6 months) history of symptomatic pericarditis.
Evidence of cardiovascular risk including any of the following: Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system (NYHA); Uncontrolled hypertension.
Evidence of cardiovascular risk including any of the following: a. Corrected QT (QTc) interval >=470 millisecond (msec); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system; Uncontrolled hypertension.
Impaired cardiac function or clinically significant cardiac disease, as defined: a) left ventricular ejection fraction < lower limit of normal (LLN) on multiple gated acquisition scan (MUGA) or echocardiogram; b) congenital long QT syndrome or family history of unexpected sudden cardiac death; c) corrected QT (QTc) corrected with Bazett’s formula (QTcB) >= 480 ms.; d) history or evidence of current clinically significant uncontrolled arrhythmias; note subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible; e) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; f) history or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA); g) treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy; h) patients with intra-cardiac defibrillators
Cardiac abnormalities as evidenced by any of the following: Baseline QT interval corrected for heart rate by Fridericia's formula (QTcF) interval >=450 milliseconds (msec), clinically significant conduction abnormalities or arrhythmias, such as subjects with second degree (Type II) or third degree atrio-ventricular block, history or evidence of current ?Class II congestive heart failure as defined by New York Heart Association (NYHA), history of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Subjects with a history of stent placement requiring ongoing anti-coagulant therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll, known cardiac metastasis.
History or evidence of cardiovascular risks, except stable ECD cardiac lesion, including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
History or evidence of cardiovascular risk including any of the following:\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators
History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < lower limit of normal (LLN)\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula Fridericia corrected QT interval (QTcB) >= 480 msec (>= 500 msec for subjects with bundle branch block)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* Other clinically significant electrocardiogram (ECG) abnormalities including second (2nd) degree (type II) or third (3rd) degree atrioventricular (AV) block\r\n* Subject with intra-cardiac defibrillators or pacemakers\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases
History or evidence of cardiovascular risks including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
History or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases
Patient must not have any history or evidence of cardiovascular risk including any of the following:\r\n* QT interval corrected by Bazett's formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Intra-cardiac defibrillator or permanent pacemaker\r\n* Cardiac metastases
Patients with a history or evidence of cardiovascular risk, including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN)\r\n* Bazett's corrected QT (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias\r\n* Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible\r\n* History of (within 6 months prior to randomization) acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases
Cardiac abnormalities as evidenced by any of the following: History or current \untreated\ clinically significant uncontrolled arrhythmias; Clinically significant conduction abnormalities or arrhythmias, subjects with Bundle Branch Block; Presence of cardiac pacemaker; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction ), coronary angioplasty, or stenting within the past 3 months.
Cardiac abnormalities as evidenced by any of the following: History of or current \untreated\ clinically significant uncontrolled arrhythmias, Clinically significant conduction abnormalities or arrhythmias, Presence of cardiac pacemaker, History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA), History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Subjects with a history of stent placement requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll.
History or evidence of cardiovascular risk including any of the following:\r\n* A corrected QT interval using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage (exception: patients with chronic atrial fibrillation with heart rate less than 100 for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to randomization\r\n* Current class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive therapy
History or evidence of cardiovascular risk including any of the following:\r\n* Corrected QT using Fridericia's formula (QTcF) >= 480 msec (>= 500 msec for subject with bundle branch block)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)
History or evidence of cardiovascular risk including any of the following: Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrolment; clinically significant uncontrolled arrhythmias; however, subjects with controlled atrial fibrillation for >30 days prior to enrollment are eligible; class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) criteria; left ventricular ejection fraction (LVEF) below the institutional LLN. If a LLN does not exist at an institution, then use LVEF <50%; abnormal cardiac valve morphology (?Grade 2) documented by ECHO; however, subjects with Grade 1 abnormalities (i.e., mild regurgitation/stenosis) may be entered on study but subjects with moderate valvular thickening should NOT be enrolled; corrected QT (QTc) interval for heart rate using Bazett-corrected QT interval (QTcB) >=480 msec; intracardiac defibrillator; treatment-refractory hypertension defined as a blood pressure (BP) >140/90 mmHg which may not be controlled by anti-hypertensive medication(s) and/or lifestyle modifications
History or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti- hypertensive therapy
History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; or history of known cardiac arrhythmias unless it has been stably controlled
Patients must not have a history of acute coronary syndromes (including unstable angina), myocardial infarction within 6 months, coronary angioplasty, or stenting within the past 24 weeks; class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; or history of known cardiac arrhythmias (such as atrial fibrillation) unless it has been stably controlled for > 30 days prior to registration; abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis]) can be entered on study; subjects with moderate valvular thickening are not eligible
History or evidence of cardiovascular risk including any of the following:\r\n* Corrected QT using Bazett's method (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to enrollment are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Cardiac metastases
History or evidence of cardiovascular risk including any of the following: \r\n* Corrected QT (QTc) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias \r\n** Exception: subjects with controlled atrial fibrillation for > 30 days prior to D1 of study treatment are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study entry\r\n* Patients with history of hypertension MUST have hypertension adequately controlled (BP < 140/90) with appropriate anti-hypertensive therapy or diet prior to study entry\r\n**Note: To be eligible a subject must have an average of BP below < 140/90 based on 3 separate measures; if the subject has a record of BP recordings taken at home and in their medical record, =< 20% of BPs taken should have numbers > 140/90\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
A history or evidence of cardiovascular risk including any of the following: Corrected QT (QTc) interval >=480 msecs History of acute coronary syndromes (including myocardial infarction or unstable angina) within 6 months prior to first dose of study treatment Coronary angioplasty, or stenting within the past 24 weeks; A history or evidence of current Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) guidelines; Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by antihypertensive therapy; Abnormal cardiac valve morphology ( >=Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study; Patients with intra-cardiac defibrillators A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible. Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc.), psychological, familial, sociological, or geographical conditions that interfere with the subject's safety or obtaining informed consent or do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol;
Any of the following cardiac abnormalities or history: a) clinically significant abnormal 12-lead electrocardiogram (ECG), QT interval (Bazett's corrected QT [QTCB]) > 480 ms, b) inability to measure QT interval on ECG, c) personal or family history of long QT syndrome, d) implantable pacemaker or implantable cardioverter defibrillator, e) resting bradycardia < 55 beats/min, f) history or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible, g) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting, within 6 months prior to randomization, h) history or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA), i) treatment refractory hypertension defined as a blood pressure of systolic > 140 mm Hg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy, j) cardiac metastases
History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < institutional LLN or < 50%\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to study dose are eligible)\r\n* Patient with symptomatic bradycardia, or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, second (2nd) degree atrioventricular (AV) block (Mobitz type 2)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study dose\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
Cardiac exclusion criteria: History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months prior to first dose of study drug; QTcF> 450 milliseconds (msec); Uncontrolled arrhythmias. Subjects with rate controlled atrial fibrillation for >1 month prior to first dose of study drug may be eligible; Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
A history or evidence of cardiovascular risk including any of the following: A QT interval corrected for heart rate using the Fridericia's formula (QTcF) >=480 millisecond (msec); A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for >30 days prior to Study Day 1 (Parts 1 and 2) or randomization (Part 3); History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to Study Day 1 (Parts 1 and 2) or randomization (Part 3); A history or evidence of current >=Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; Treatment refractory hypertension defined as a blood pressure of systolic>140 millimeters of mercury (mmHg) and/or diastolic >90 mmHg which cannot be controlled by anti-hypertensive therapy; Patients with intra-cardiac defibrillators or permanent pacemakers; Known cardiac metastases.
History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
The following cardiac abnormalities: Corrected QT (QTc) interval >=480 millisecond. History of acute coronary syndromes (including unstable angina) within the past 24 weeks Coronary angioplasty or stenting within the past 24 weeks. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. Abnormal cardiac valve morphology (>= Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). History of known arrhythmias (except sinus arrhythmia and atrial fibrillation that is controlled) within the past 24 weeks.
History or evidence of cardiovascular risk including any of the following: Clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block; history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within the past 6 months prior to enrolment, Class III or IV heart failure as defined by the New York Heart Association functional classification system, LVEF below 50%; known cardiac metastases
A history or evidence of cardiovascular risk including: a QT interval corrected for heart rate using the Bazett's formula (QTcB) >=480 msec; a history or evidence of current clinically significant uncontrolled arrhythmias (clarification: Subjects with atrial fibrillation controlled for >30 days prior to dosing are eligible); a history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; a history or evidence of current >=Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; subjects with intra-cardiac defibrillators; abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study. Subjects with prosthetic valves can be considered eligible provided they meet the criteria as stated above; Treatment refractory hypertension defined as a blood pressure of systolic >140 millimeter of mercury (mmHg) and/or diastolic >90 mmHg (or above 95th age-specific percentile listed in protocol), which cannot be controlled by anti-hypertensive therapy.
A history or evidence of cardiovascular risk including any of the following:\r\n* A corrected QT (QTc) interval >= 500 ms at screening\r\n* A history or evidence of current clinically significant uncontrolled arrhythmias\r\n** Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible\r\n* A history (within 6 months prior to randomization) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty\r\n* A history or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 100 mm Hg which cannot be controlled by antihypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers
Evidence of cardiovascular risk including any of the following: QT interval corrected>=470 millisecond, evidence of current clinically significant uncontrolled arrhythmias, history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening, Class III or IV heart failure as defined by the New York Heart Association functional classification system, uncontrolled hypertension, subjects with intra-cardiac defibrillators or permanent pacemakers, abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula corrected QT (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases
History or evidence of cardiovascular risk including any of the following:\r\n* Corrected QT (QTc) interval >= 480 msecs\r\n* Clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to day 1 of treatment with GSK1120212 are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 24 weeks\r\n* >= class II heart failure as defined by the New York Heart Association (NYHA) functional classification system