A Phase 1, Single Center Double-blind, Randomized, Placebo-controlled Study to Evaluate the Pharmacokinetics and Safety of Omecamtiv Mecarbil in Healthy Japanese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Dosing Period 1: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of omecamtiv mecarbil in healthy volunteers in Japan.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •No history or evidence of clinically relevant medical disorders as determined by the Investigator, and in good health as determined by a pre-study physical examination and medical history with no clinically significant abnormalities, normal vital signs and no history or presence of a clinically significant abnormal electrocardiogram finding
- •Subjects' pre-study clinical laboratory findings (including creatine phosphokinase) should be within normal range or if outside of the normal range, are deemed not clinically significant by the Investigator.
排除标准
- •A clinically significant disorder/disease, including gastro intestinal abnormalities that might interfere with absorption
- •An unstable medical condition, defined as having been hospitalized within 28 days before day 1, major surgery within 6 months before day 1, or otherwise unstable in the judgment of the Investigator
- •History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
- •History of malignancy of any type other than surgically excised non-melanomatous skin cancers or in situ cervical cancer within 5 years before the day of dosing
- •Use of any prescription or over-the-counter medications within 14 days or 5 half-lives (whichever time period is greater), prior to receiving the first dose of omecamtiv mecarbil (acetaminophen up to 2 grams per day for analgesia and hormone replacement therapy (e.g., estrogen) will be allowed
- •Use of any known inhibitors of CYP3A4/p-glycoprotein (P-gp) or CYP2D6 within 14 days or 5 half-lives, whichever is longer; or use of grapefruit juice or grapefruit containing products within 7 days prior to receiving the first dose of omecamtiv mecarbil
- •Use of any known CYP3A4 inducers within 30 days or 5 half-lives, whichever is longer, before receiving omecamtiv mecarbil
研究组 & 干预措施
Placebo
Participants received placebo tablets twice a day (BID) in dosing period 1 (days 1 to 8) and in dosing period 2 (days 20 to 27).
干预措施: Placebo (Drug)
Omecamtiv mecarbil 25 mg / 37.5 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg or 37.5 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose): If day 8 Cpredose was < 200 ng/mL, participants received 37.5 mg BID; if day 8 Cpredose was ≥ 200 ng/mL or a day 8 PK value was not available participants continued to receive 25 mg BID.
干预措施: Omecamtiv mecarbil (Drug)
Omecamtiv mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg or 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose): If day 8 Cpredose was < 200 ng/mL, participants received 50 mg BID; if day 8 Cpredose was ≥ 200 ng/mL or a day 8 PK value was not available participants continued to receive 25 mg BID.
干预措施: Omecamtiv mecarbil (Drug)
结局指标
主要结局
Dosing Period 1: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
时间窗: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
Dosing Period 2: AUC(0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 2
时间窗: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
Dosing Period 2: Accumulation Ratio
时间窗: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
Accumulation ratio calculated as the ratio of day 27 AUC(0-12) / day 20 AUC(0-12).
Dosing Period 1: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
时间窗: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
Dosing Period 1: Area Under the Concentration-time Curve for a Dosing Interval of 12 Hours (AUC0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 1
时间窗: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
Dosing Period 1: Predose Omecamtiv Mecarbil Plasma Concentration
时间窗: Day 8 predose
Dosing Period 1: Accumulation Ratio
时间窗: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
Accumulation ratio calculated as the ratio of day 8 AUC(0-12) / day 1 AUC(0-12)
Dosing Period 2: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
时间窗: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
Dosing Period 2: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
时间窗: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
Dosing Period 2: Predose Omecamtiv Mecarbil Plasma Concentration
时间窗: Day 27 predose
次要结局
- Number of Participants With Treatment-emergent Adverse Events(35 days)
- Number of Participants With Grade 3 or Higher Laboratory Toxicities(35 days)
- Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2(Day 20 predose and Day 27)
- Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1(Day 1 predose and day 8)