Safety, PK, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction
Phase 2
Completed
- Conditions
- Heart Failure With Reduced Ejection Fraction
- Interventions
- Drug: 25 mg Omecamtiv MecarbilDrug: PlaceboDrug: 37.5 mg Omecamtiv MecarbilDrug: 50 mg Omecamtiv Mecarbil
- Registration Number
- NCT02695420
- Lead Sponsor
- Cytokinetics
- Brief Summary
* To evaluate pharmacokinetics (PK) of omecamtiv mecarbil in Japanese subjects with heart failure (HF) with reduced ejection fraction
* To evaluate the safety and tolerability of oral omecamtiv mecarbil
- Detailed Description
This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
Inclusion Criteria
- Japanese male or female ≥ 20 years and ≤ 85 years of age
- History of chronic stable heart failure (HF) with reduced ejection fraction, defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
- Treated for HF with optimal pharmacological therapy
- Left ventricular ejection fraction ≤ 40% at screening
Exclusion Criteria
- Severe uncorrected valvular heart disease
- 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 (BP) > 160 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg, or heart rate (HR) > 110 beats per minute (bpm) or HR < 50 bpm
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
- Total bilirubin (TBL) ≥ 2x upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x ULN Other Exclusion Criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 50 mg Omecamtiv Mecarbil BID Target Dose 25 mg Omecamtiv Mecarbil Participants will receive Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK. 37.5 mg Omecamtiv Mecarbil BID Target Dose 25 mg Omecamtiv Mecarbil Participants will receive omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK. Placebo BID 25 mg Omecamtiv Mecarbil Participants will receive placebo BID. 37.5 mg Omecamtiv Mecarbil BID Target Dose 37.5 mg Omecamtiv Mecarbil Participants will receive omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK. 25 mg Omecamtiv Mecarbil BID Placebo Participants will receive 25 mg omecamtiv mecarbil BID. 50 mg Omecamtiv Mecarbil BID Target Dose 50 mg Omecamtiv Mecarbil Participants will receive Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK.
- Primary Outcome Measures
Name Time Method PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8) Week 8 (Day 56) at predose, at 2 hours ±30 minutes; 4 hours ±30 minutes; 6 hours ±30 minutes; 8 hours ±30 minutes after morning dose Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
- Secondary Outcome Measures
Name Time Method Change From Baseline at Week 16 in Systolic Ejection Time (SET) Baseline, Week 16 (Day 112) LS mean was from the repeated measures model, which included treatment group, stratification factor (from IVRS), scheduled visit, baseline value, and the interaction of treatment group with scheduled visit as covariates.
Trial Locations
- Locations (1)
Research Site
🇯🇵Shinagawa-ku, Tokyo, Japan