A Randomized, 2-Part, Single-Dose, Crossover Study to Evaluate the Effect of Aficamten Administration on QT/QTc Interval in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Part A: To determine the dose for Part B
研究概览
简要总结
This is a single-center, 2-part (Part A and Part B) study in healthy participants. Part A (Dose Finding) is an open-label, SAD study to identify the dose for Part B. Part B (TQT Study) is a randomized, double-blind (with respect to aficamten and matching placebo), positive- and placebo-controlled, single-dose, 3-way crossover study to evaluate the effect of aficamten administration on QT/QTc interval.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male or female, 18-45 years of age, inclusive, at the screening visit.
- •Continuous non-smoker who has not used nicotine- and tobacco -containing products for at least 3 months prior to the first dosing based on participant self- reporting.
- •Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 at the screening visit.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the PI or designee, including the following:
- •Supine blood pressure is ≥ 90/40 mmHg and ≤ 140/90 mmHg at the screening visit.
- •Oxygen saturation (SpO2) is ≥ 95% at the screening visit.
- •Liver function tests (e.g., bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]) considered not clinically significant in the opinion of the PI or designee at the screening visit.
- •Estimated creatinine clearance ≥ 90 mL/min at the screening visit.
- •No clinically significant history and presence of ECG findings as judged by the PI or designee at the screening visit and first check-in, including each of the following:
- •HR between 50 bpm and 100 bpm, inclusive.
- •QTcF interval is ≤450 msec (males) and ≤460 msec (females).
- •QRS ≤110 msec; if >110 msec, result will be confirmed by a manual over read.
- •PR ≤220 msec.
- •LVEF ≥65% at the screening visit.
排除标准
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- •History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
研究组 & 干预措施
Part A (Dose Finding Cohort 1): Aficamten 50 mg
Participants in this arm will receive a single oral dose of 50 mg aficamten.
干预措施: Aficamten (Drug)
Part A (Dose Finding Cohort 2): Aficamten 75 mg
Participants in this arm will receive a single oral dose up to 75 mg aficamten.
干预措施: Aficamten (Drug)
Part A (Dose Finding Cohort 3): Aficamten 100 mg
Participants in this arm will receive a single oral dose up to 100 mg aficamten.
干预措施: Aficamten (Drug)
Part B (TQT Study): Aficamten
Participants will receive a single oral dose of aficamten. The dose will be determined based on review of Part A PK parameters, echocardiogram parameters, safety, and tolerability for aficamten.
干预措施: Aficamten (Drug)
Part B (TQT Study): Aficamten-matching Placebo
Participants in this arm will receive a single oral dose of aficamten-matching placebo.
干预措施: Aficamten-matching Placebo (Drug)
Part B (TQT Study): Moxifloxacin 400 mg
Participants will receive a single oral dose of 400 mg moxifloxacin
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Part A: To determine the dose for Part B
时间窗: Baseline to End of Study, up to 8 weeks
To determine the dose for Part B based on Part A PK and safety data.
Part B: placebo-corrected dQTcF for aficamten
时间窗: Baseline to End of Study, up to 14.5 weeks
To evaluate the effect of a single oral dose of aficamten on the QTc interval in healthy participants.
次要结局
- Part B: placebo-corrected dQTcF for moxifloxacin(Baseline to End of Study, up to 14.5 weeks)