Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (New York Heart Association [NYHA] class >= 3 or left ventricular ejection fraction < 45%), unstable angina pectoris, myocardial infarction within the last 3 months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st 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; 1st 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 >= 3, or\r\n* myocardial infarction (mi) within 3 months
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st 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 >= 3, or \r\n* Myocardial infarction (MI) within 6 months\r\n* Left ventricular ejection fraction < 40 %\r\n* Hypertension > 160 mm Hg systolic or > 100 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; 1st 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 3, or myocardial infarction (MI) within 3 months; left ventricular ejection fraction < 40%; hypertension > 140 millimeter of mercury (mm Hg) systolic or > 90 mm Hg diastolic with or without antihypertensive therapy
Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded); or
Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (i.e.: ventricular tachycardia on antiarrhythmics are excluded and first [1st] 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 >= 3, or myocardial infarction (MI) within 3 months
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st 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 >= 3, or\r\n* Myocardial infarction (MI) within 3 months
Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmics are excluded, 1st degree AV block or asymptomatic LAFB/RBBB are eligible)
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or \r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st 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 >= 3, or\r\n* Myocardial infarction (MI) within 3 months
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmics are excluded and 1st 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 >= 3, or\r\n* Myocardial infarction (MI) within 3 months
Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and 1st 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 >= 3, or\r\n* Myocardial infarction (MI) within 3 months of cycle 1 day 1 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 (1st) 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 >= 3, or\r\n* Myocardial infarction (MI) within 3 months of initiation of therapy
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 [1st] 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 3, or\r\n* Myocardial infarction (MI) within 3 months
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 1st 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 >= 3, or myocardial infarction (MI) within 3 months of consent date
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
Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG), e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, QT interval corrected by Fridericia’s formula (QTcF) of >= 450 ms in males or >= 470 ms in females
Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250msec).
Clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
Any clinically important abnormalities in rhythm, conduction or morphology of a resting ECG, e.g., complete left bundle branch block, third degree heart block, that in the opinion of the Investigator render the patient unsuitable for participation in the study
Any of the following cardiac criteria:\r\n* Mean resting corrected QT interval (QTc using Frederica’s formula [QTcF]) > 470 msec\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\r\n* Congenital long QT syndrome or family history of long QT syndrome
Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)
Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting Electrocardiograms, e.g., complete left bundle branch block, third degree heart block
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG
Any clinically relevant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec).
Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec.
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block
Has any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms)
Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded
Right bundle branch block + left anterior hemiblock (bifascicular block)
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 > 450 msec prior to randomization.
Complete left bundle branch or bifascicular block.
No presence of left bundle branch blocks (LBBB)
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
Significant uncontrolled cardiac arrhythmias, including ventricular arrhythmias, congenital long QT syndrome, symptomatic atrial fibrillation, symptomatic bradycardia, right bundle branch block plus left anterior hemiblock or bifasicular block
Electrocardiogram (ECG) abnormalities:\r\n* Prolonged corrected QT (QTc) (Bazette’s or Fredericia’s correction) interval on screening ECG (>= 450 msec)\r\n* QRS ? 120 msec\r\n* PR ? 210 msec\r\n* Any prior history, or current evidence of second- or third-degree heart block\r\n* Heart rate ? 40 beats per minute at screening\r\n* ECG second degree heart block (Mobitz’s type 2 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
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
Right bundle branch block and left anterior hemiblock (bifascicular block)
Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (< 50 beats per minutes)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)
Known congestive heart failure and/ or a known decreased cardiac ejection fraction of < 45%. A baseline QT interval as corrected by Fridericia's formula (QTcF) > 480 msec, a complete left bundle branch block (defined as a QRS interval ? 120 msec in left bundle branch block form) or an incomplete left bundle branch block.
Any electrocardiograph (ECG) changes that interfere with QT interval interpretation (e.g., left bundle branch block, frequent premature ventricular contractions)
DOSE EXPANSION COHORT: History or presence of an abnormal ECG which, in the investigator's opinion, is clinically meaningful; screening QTcF interval > 480ms is excluded; subjects with left bundle branch block are excluded
Complete left bundle branch block
Right bundle branch block + left anterior hemiblock (bi-fascicular block)
History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
Abnormal ECGs that are clinically significant such as QT prolongation (QTc > 480 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
Complete left bundle branch block (LBBB)
Clinically significant cardiac arrhythmias, complete left bundle branch block, high-grade AV block
Complete left bundle branch, or bifasicular block.
Abnormal ECGs that are clinically significant such as QT prolongation (QTc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block or existing left bundle branch block, or signs of new, active ischemia.
A baseline QT interval as corrected by Fridericia's formula (QTcF) > 450 msec, a complete left bundle branch block (defined as a QRS interval ? 120 msec in left bundle branch block form) or an incomplete left bundle branch block.
Complete left bundle branch block
Right bundle branch block + left anterior hemiblock (bifascicular block)
Right bundle branch block + left anterior hemiblock (bifascicular block)
Right or left bundle branch block
Complete left bundle branch or bifascicular block
Complete left bundle branch, or bifasicular, block.
Right bundle branch block + left anterior hemiblock (bifascicular block)
Right bundle branch block + left anterior hemiblock (bifascicular block).
A baseline QT interval as corrected by Fridericia's formula (QTcF) > 450 msec, a complete left bundle branch block (defined as a QRS interval ? 120 msec in left bundle branch block form) or an incomplete left bundle branch block.
Bundle branch block or QRS ? 120 msec
Complete left bundle branch block
Right bundle branch block and left anterior hemi block (bifascicular block)
Presence of left bundle branch block (LBBB)
Complete left bundle branch block
Right bundle branch block and left anterior hemiblock (bifascicular block)
Complete left bundle branch block;
Complete left bundle branch block;
Right bundle branch block + left anterior hemiblock (bifascicular block)
Presence of left bundle branch block (LBBB);
Presence of left bundle branch block (LBBB)
Patients with left bundle branch block (LBBB) and/or artificial pacemaker
Impaired cardiac function including any one of the following: complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (< 50 beats per minute), QT interval corrected by Fridericia's formula (QTcF) > 450 msec on screening electrocardiogram (ECG), or right bundle branch block + left anterior hemiblock (bifascicular block)
Complete left bundle branch block
Right bundle branch block plus left anterior or posterior hemiblock