A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)
研究概览
简要总结
- 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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Placebo BID
Participants will receive placebo BID.
干预措施: 25 mg Omecamtiv Mecarbil (Drug)
25 mg Omecamtiv Mecarbil BID
Participants will receive 25 mg omecamtiv mecarbil BID.
干预措施: Placebo (Drug)
37.5 mg Omecamtiv Mecarbil BID Target Dose
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.
干预措施: 25 mg Omecamtiv Mecarbil (Drug)
37.5 mg Omecamtiv Mecarbil BID Target Dose
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.
干预措施: 37.5 mg Omecamtiv Mecarbil (Drug)
50 mg Omecamtiv Mecarbil BID Target Dose
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.
干预措施: 25 mg Omecamtiv Mecarbil (Drug)
50 mg Omecamtiv Mecarbil BID Target Dose
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.
干预措施: 50 mg Omecamtiv Mecarbil (Drug)
结局指标
主要结局
PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)
时间窗: 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
时间窗: Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
次要结局
- Change From Baseline at Week 16 in Systolic Ejection Time (SET)(Baseline, Week 16 (Day 112))