RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:* QT interval corrected for heart rate using the Bazetts formula QTcB >= 480 msec at baseline * History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration* 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* Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)* Intra-cardiac defibrillator* 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* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible* 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
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:* Left ventricular ejection fraction (LVEF) < LLN* A QT interval corrected for heart rate using the Bazetts formula corrected QT (QTcB) >= 480 msec* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* Known cardiac metastases
History or evidence of cardiovascular risks including any of the following:* QT interval corrected for heart rate using the Bazetts formula QTcB >= 480 msec* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system* Intra-cardiac defibrillators* 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* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible* 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:* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system* Intra-cardiac defibrillators* 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* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible* 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:* A QT interval corrected for heart rate using the Bazetts formula QTcB >= 480 msec on screening electrocardiography (ECG)* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* 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:* LVEF < LLN* A QT interval corrected for heart rate using the Bazetts formula QTcB >= 480 msec* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* Patients with intra-cardiac defibrillators * Known cardiac metastases
History or evidence of cardiovascular risk including any of the following:* Left ventricle ejection fraction (LVEF) < LLN* A QT interval corrected for heart rate using the Bazetts formula QTcB >= 480 msec* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to enrollment are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* Known cardiac metastases* Patients with intra-cardiac defibrillators
History or evidence of cardiovascular risk including any of the following:* An average of the three most recent QT intervals corrected for heart rate using the Bazetts formula QTcB >= 460 msec* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* 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* Prior placement of an implantable defibrillator* History of or identification on screening imaging of intracardiac metastases
Patients with a history or evidence of cardiovascular risk, including any of the following:* Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN)* Bazett's corrected QT (QTcB) >= 480 msec* History or evidence of current clinically significant uncontrolled arrhythmias* Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible* History of (within 6 months prior to randomization) acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)* 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* Patients with intra-cardiac defibrillators or permanent pacemakers* Known cardiac metastases
History or evidence of cardiovascular risk including any of the following:* Left ventricular ejection fraction (LVEF) < LLN* A QT interval corrected for heart rate using the Bazetts formula (QTcB) >= 480 msec* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* Patients with intra-cardiac defibrillators* Known cardiac metastases
Patients must not have a history of or evidence of cardiovascular risks including any of the following:* QT interval corrected for heart rate using the Bazetts formula (QTcB) >= 480 msec. at baseline* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration* 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* Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multi gated acquisition scan (MUGA)* Intra-cardiac defibrillator* 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* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible* 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, except stable ECD cardiac lesion, including any of the following:* QT interval corrected for heart rate using the Bazetts formula (QTcB) >= 480 msec* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system* Intra-cardiac defibrillators* 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* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible* 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:* LVEF < LLN (lower limit of normal range)* A QT interval corrected for heart rate using the Bazetts formula QTcB >= 480 msec* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system* 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* Patients with intra-cardiac defibrillators* Known cardiac metastases