Phase 2
N=544
COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure
Modified Release Oral Formulation · Left Ventricular Systolic Dysfunction · Chronic Heart Failure · History of Chronic Heart Failure · Left Ventricular Ejection Fraction
Bottom Line
View on ClinicalTrials.gov: NCT01786512 ↗Enrolled (actual)
544
Serious AEs
18.9%
Results posted
May 2021
Primary outcome: Primary: Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7) — 193; 201; 171; 492 ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Omecamtiv Mecarbil Matrix F1 Formulation (Drug); Omecamtiv Mecarbil Matrix F2 Formulation (Drug); Placebo (Drug); Omecamtiv Mecarbil Swellable Core Technology F2 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Cytokinetics
- Primary completion
- Jul 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7) |
193; 201; 171; 492; 502; 601 | — |
| PRIMARY Dose Escalation Phase: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7) |
3.9; 2.0; 4.2; 2.6; 2.2; 4.6 | — |
| PRIMARY Dose Escalation Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing on Day 7 |
157; 137; 134; 376; 395; 476 | — |
| PRIMARY Dose Escalation Phase: Area Under the Plasma Concentration-time Curve for a Dosing Interval of 12 Hours Post Dose (AUC12) for Omecamtiv Mecarbil |
2030; 2000; 1740; 5070; 5010; 6550 | — |
| PRIMARY Expansion Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing |
174; 179; 156; 161; 165; 263 | — |
| PRIMARY Expansion Phase: Maximum Observed Plasma Concentration of Omecamtiv Mecarbil |
212; 212; 200; 318 | — |
| SECONDARY Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20 |
0.0000; 0.0112; 0.0250 | 0.0007 sig |
| SECONDARY Expansion Phase: Change From Baseline in Stroke Volume at Week 20 |
-1.05; 3.53; 2.58 | 0.0036 sig |
| SECONDARY Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20 |
-0.242; -0.322; -0.421 | 0.1732 |
| SECONDARY Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20 |
0.089; 0.023; -0.040 | 0.1899 |
| SECONDARY Expansion Phase: Change From Baseline in Heart Rate at Week 20 |
0.57; -0.77; -2.40 | 0.2177 |
| SECONDARY Expansion Phase: Change From Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) at Week 20 |
502; -319; -468 | 0.0205 sig |
| SECONDARY Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events |
4; 2; 6; 6; 1; 9 | — |
| SECONDARY Expansion Phase: Number of Participants With Treatment-emergent Adverse Events |
91; 92; 95; 62; 60; 61 | — |
Summary
The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment.
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
- 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
Data sourced from ClinicalTrials.gov (NCT01786512). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.