History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past weeks. Acute coronary syndrome within months prior to starting treatment Recent (within months) history of second degree (Type II) or third degree atrioventricular (AV) block cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting; Class II, III, or IV heart failure, or symptomatic pericarditis. Acute coronary syndrome Cardiac abnormalities:\r\n* Mean QTc interval >= msec at screening\r\n* Acute coronary syndrome (ACS)/acute myocardial infarction (AMI) within weeks prior to screening\r\n* Percutaneous coronary intervention (PCI)/percutaneous transluminal coronary angioplasty (PTCA) within weeks prior to screening\r\n* Symptomatic heart failure New York Heart Association (NYHA) class >= II symptoms Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting\r\n* Coronary angioplasty, or stenting) or symptomatic pericarditis within months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction < % as determined by multigated acquisition (MUGA) scan or echocardiography (ECHO) (MUGA and ECHO are not required prior to enrollment) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stent placement within months prior to study drug dosing Any other significant medical condition not under control, including any acute coronary syndrome within the past months Significant cardiovascular risk including, but not limited to, recent (within weeks) coronary stenting or myocardial infarction within months History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within months prior to registration. Inpatient admission to a hospital for unstable angina or myocardial infarction within the last months prior to first dose or percutaneous cardiac intervention with recent stent within months or coronary artery bypass grafting within months Myocardial infarction, stroke, coronary artery bypass surgery, coronary stent, or unstable angina within one year are excluded; Note: A subject may enroll in the study and have a start date set in the near future in a way that meets the timelines for exclusion items by the treatment start date Significant cardiovascular risk including, but not limited to, recent (within weeks) coronary stenting or myocardial infarction within months history of acute coronary syndromes (including unstable angina) Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < months prior to screening\r\n* Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia Patients experiencing a cardiac events (acute coronary syndrome, myocardial infarction, or ischemia) within the months prior to accrual Has significant cardiac conduction abnormalities and/ or pacemaker or any of the following criteria:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting) < months prior to screening\r\n* Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening\r\n* Uncontrolled arterial hypertension, defined as blood pressure (BP) > / mmHg (average of consecutive readings) Patients have clinically significant cardiovascular disease, including any of the following: \r\n* History of acute coronary syndrome including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty or stenting < months prior to screening\r\n* Symptomatic chronic heart failure (New York Heart Association criteria, class II-IV)\r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT) Patient do not have adequate cardiac function defined as:\r\n* Left ventricular ejection fraction (LVEF) =< % as determined by a multigated acquisition (MUGA) scan or echocardiogram\r\n* Corrected QT (QTc) interval >= ms\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < months prior to screening\r\n* Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening History or evidence of cardiovascular (CV) risk including any of the following: a) Recent (within the past 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 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 months) history of symptomatic pericarditis. Acute coronary syndrome, or any form of coronary revascularization procedure (including coronary artery bypass grafting [CABG]), within months of screening. History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past months. History of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following within months of enrollment: myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting, symptomatic chronic heart failure, clinically significant cardiac arrhythmias and/or conduction (except atrial fibrillation and paroxysmal supraventricular tachycardia) History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within months prior to enrollment History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting) < months prior to screening Impaired cardiovascular function or clinically specific cardiovascular disease including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) =< months; OR\r\n* Symptomatic chronic heart failure history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < months prior to screening; except atrial fibrillation and paroxysmal supraventricular tachycardia Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis Subject has a high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within months prior to screening Patients have clinically significant cardiovascular disease, including any of the following \r\n* Any history of acute coronary syndrome including myocardial infarction, stable or unstable angina, coronary artery bypass grafting (CABG), coronary angioplasty or stenting, or known obstructive coronary artery disease\r\n* Symptomatic chronic heart failure (New York Heart Association criteria, class II-IV) \r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT) History of acute coronary syndromes (including myocardial infarction and angina), coronary angioplasty, or stenting within months prior to enrollment. History or evidence of cardiovascular risk including any of the following -- History of acute coronary syndromes (including myocardial infarction and angina), coronary angioplasty, or stenting within months prior to enrollment. Additional Exclusion Criteria for Part E History or evidence of cardiac risk, including:\r\n* Corrected QT interval on screening electrocardiogram (ECG) > msec\r\n* Left ventricular ejection fraction (LVEF) < %\r\n* Clinically significant uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia\r\n* History of acute coronary syndromes within months prior to the first dose of study therapy (including myocardial infarction and unstable angina, coronary artery bypass graft, angioplasty, or stenting) Patients have clinically significant cardiovascular disease, including any of the following:\r\n* History of acute coronary syndrome including myocardial infarction, unstable angina, coronary artery bypass surgery (CABG), coronary angioplasty or stenting < months prior to screening\r\n* Symptomatic chronic heart failure (New York Heart Association Criteria, class II-IV)\r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, and/or stenting up to weeks before Cycle , Day Stroke, transient ischemic attack, arterial embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within the past months History of acute coronary syndromes (specifically, myocardial infarction and unstable angina), severe/unstable angina, coronary angioplasty, or stenting within months prior to the initiation of therapy on this protocol History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or coronary artery stenting within the past months History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within months prior to study enrollment Any other significant medical condition not under control, including any acute coronary syndrome within the past months Known myocardial infarction, severe/unstable angina, percutaneous transluminal coronary angioplasty/stenting (PTCA), or coronary artery bypass graft (CABG) within month of the first dose of the study treatment Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < months prior to screening\r\n* Symptomatic chronic heart failure\r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia High cardiovascular risk, including but not limited to, recent coronary stenting or myocardial infarction in the past year Myocardial infarction, unstable angina, coronary artery bypass graft, coronary artery angioplasty or stent placement within months before scheduled dosing day ; Active coronary artery disease, defined as myocardial infarction, unstable angina, coronary bypass graft, or stenting within months prior to study entry A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within months prior to randomization History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < months prior to screening A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within months prior to randomization Coronary angioplasty or stenting within the past weeks Recent acute coronary syndrome (ACS)/acute myocardial infarction (AMI) defined as within weeks prior to screening Recent percutaneous coronary intervention (PCI)/percutaneous transluminal coronary angioplasty (PTCA) defined as within weeks prior to screening A history (within months prior to first dose of study treatment) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty History of acute coronary syndromes. 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 months prior to enrolment, Class III or IV heart failure as defined by the New York Heart Association functional classification system, LVEF below %; known cardiac metastases History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past weeks. Acute coronary syndrome Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < months prior to screening,\r\n* Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia No unstable angina, myocardial infarction, or coronary angioplasty within the past months or an untreated cardiac dysrhythmia Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within months Acute coronary event within the past month Acute coronary (e.g. myocardial infarction) or vascular event within the last year as well as uncontrolled coronary heart disease (e.g. progressive angina) Individuals with history of myocardial infarction, stroke, coronary-artery bypass draft, invasive coronary revascularization in the preceding years Patients who have experienced an acute coronary syndrome or angina in the past months Patients who have undergone coronary artery bypass grafting (CABG) or coronary stenting in the past years Significant cardiovascular risk including, but not limited to, recent (within days) coronary stenting or myocardial infarction within months Acute myocardial infarctions or acute coronary syndromes Known to suffer from stable angina pectoris and/or proven coronary disease, or have symptoms suspicious of coronary disease