COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure

Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20

Systolic ejection time was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.

Time frame: Baseline and week 20

Expansion Phase: Change From Baseline in Stroke Volume at Week 20

Stroke volume was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.

Time frame: Baseline and week 20

Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20

LVESD was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.

Time frame: Baseline and week 20

Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20

LVEDD was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.

Time frame: Baseline and week 20

Expansion Phase: Change From Baseline in Heart Rate at Week 20

Heart rate was measured using electrocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.

Time frame: Baseline and week 20

Expansion Phase: Change From Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) at Week 20

Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.

Time frame: Baseline and week 20

Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events

An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. Each adverse event was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, and Grade 4 = life-threatening AE. A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: * fatal * life threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event

Time frame: From first dose of study drug to 4 weeks after last dose; treatment duration was 7 days in the dose escalation phase.

Expansion Phase: Number of Participants With Treatment-emergent Adverse Events

An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. Each adverse event was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, and Grade 4 = life-threatening AE. A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: * fatal * life threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event

Time frame: From first dose of study drug until 4 weeks after last dose; treatment duration was 20 weeks in the expansion phase.