Patients with a history of any of the following within the last 6 months prior to study entry are ineligible:* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)* Placement of a pacemaker for control of rhythm* New York Heart Association (NYHA) class III or IV heart failure* Pulmonary embolism
History of any of the following within the last 6 months prior to study entry:* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)* Placement of a pacemaker for control of rhythm* Pulmonary embolism
Ischemic myocardial event including angina requiring therapy and artery revascularization procedures
Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures
History of any of the following within the last 6 months prior to study entry:* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures  * Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) * Pulmonary embolism* New York Heart Association (NYHA) class III or IV heart failure * Placement of a pacemaker for control of rhythm
Significant active cardiovascular or pulmonary disease including:* Uncontrolled hypertension (i.e., systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed* Pulmonary hypertension* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement* History of arrhythmia requiring an implantable cardiac defibrillator* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last 6 months before administration of the first dose of drug:** Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)** Placement of a pacemaker for control of rhythm** Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures** Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures** New York Heart Association (NYHA) class III or IV heart failure** Pulmonary embolism* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTcF >= 470 msec (mean value) obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value, or history of congenital long QT syndrome, or torsades de pointes); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval* Left ventricular ejection fraction (LVEF) by either multigated acquisition (MUGA) or echocardiography (ECHO) less than lower limit of normal
Patients with a history of the following within =< 6 months of study entry are NOT eligible:* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)* New York Heart Association (NYHA) class III or IV heart failure* Pulmonary embolism