COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF)
Modified Release Oral Formulation, Left Ventricular Systolic Dysfunction, Chronic Heart Failure
About this trial
This is an interventional treatment trial for Modified Release Oral Formulation focused on measuring Pharmacokinetics, Omecamtiv mecarbil, AMG 423, Double-blind, Randomized, Placebo-controlled, Oral forumlation, CK-1827452, Cardiac myosin activator
Eligibility Criteria
Inclusion Criteria:
- History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
- Treated with stable, optimal pharmacological therapy for ≥ 4 weeks
- History of left ventricular ejection fraction (LVEF) ≤ 40%
- Elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP)
Exclusion criteria:
- Severe uncorrected valvular heart disease
- Hospitalization within 30 days prior to enrollment
- Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease
- Acute myocardial infarction, unstable angina or persistent angina at rest within 30 days prior to randomization
- Systolic blood pressure > 160 mmHg or < 90 mmHg or diastolic blood pressure > 90 mmHg
- Total bilirubin ≥ 2 x upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x ULN
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Placebo Comparator
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Dose-escalation Cohort 1: Placebo
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2
Dose-escalation Cohort 2: Placebo
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2
Expansion Phase: Placebo
Expansion Phase: Omecamtiv Mecarbil 25 mg M-F1
Expansion Phase: OM M-F1 PK-based Titration
Participants received placebo tablets twice a day (BID) for 7 days.
Participants received 25 mg omecamtiv mecarbil (OM) Matrix F1 (M-F1) tablets twice a day for 7 days.
Participants received 25 mg omecamtiv mecarbil Matrix F2 (M-F2) tablets twice a day for 7 days.
Participants received 25 mg omecamtiv mecarbil swellable core technology F2 (SCT-F2) tablets twice a day for 7 days.
Participants received placebo tablets twice a day for 7 days.
Participants received 50 mg omecamtiv mecarbil M-F1 tablets twice a day for 7 days.
Participants received 50 mg omecamtiv mecarbil M-F2 tablets twice a day for 7 days.
Participants received 50 mg omecamtiv mecarbil SCT-F2 tablets twice a day for 7 days.
Participants received placebo tablets twice a day for 20 weeks.
Participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day for 20 weeks.
All participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day. At week 8 the dose escalated to 50 mg twice a day if the week 2 predose plasma concentration of OM was less than the predefined cutoff of 200 ng/mL.