A Phase 1, Randomized, Single-Dose, Positive- and Placebo-Controlled, 3-Way Crossover Study to Evaluate the Effects of Varegacestat on Cardiac Repolarization in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Placebo-corrected change from baseline QTc and varegacestat and its metabolite, AL102 MTB, plasma concentrations
研究概览
简要总结
This clinical study is designed to study the effect of a single dose of varegacestat on cardiac repolarization in healthy adult participants.
详细描述
This is a double-blind (with respect to varegacestat and placebo only), single-dose, randomized, placebo- and positive- controlled, 3-way crossover study.
On Day 1 of each period, participants will receive one of 3 treatments: a single dose of varegacestat (Treatment A), a single dose of varegacestat matching placebo (Treatment B), or a single dose of moxifloxacin (Treatment C). In each period, cardiodynamic ECGs will be collected predose and for 24 hours postdose. PK samples will be collected predose and up to 168 hours post-dose for assessments of varegacestat and AL102 MTB, and up to 24 hours post-dose for assessment of moxifloxacin.
There will be a washout of at least 14 days between doses. Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
Double (Participant, Investigator) This is a double-blind study (with respect to varegacestat and placebo only; moxifloxacin will be open label).
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male or female (of non childbearing potential), 18 to 55 years of age, inclusive, at the screening visit.
- •Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, and vital signs, as deemed by the PI or designee
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 pose an additional risk to the participant by their participation in the study.
- •Have taken an investigational drug or participated in a clinical trial evaluating an investigational drug or device within 30 days (or 5 half-lives) prior to the study drug dose, whichever is longer.
研究组 & 干预措施
Varegacestat
干预措施: varegacestat (Drug)
Placebo
干预措施: Placebo (Drug)
Moxifloxacin
干预措施: Moxifloxacin 400 mg (Drug)
结局指标
主要结局
Placebo-corrected change from baseline QTc and varegacestat and its metabolite, AL102 MTB, plasma concentrations
时间窗: 24 hours
次要结局
- Maximum observed concentration (Cmax) of varegacesatat and AL102-MTB (varegacestat metabolite).(7 days)
- Change from baseline, placebo-corrected, and categorical outliers of the ECG parameter HR from a single oral dose of varegacestat.(24 hours)
- Change from baseline and placebo-corrected ECG parameter QT from a single oral dose of varegacestat.(24 hours)
- Change from baseline, placebo-corrected, and categorical outliers of the ECG parameter QTcF from a single oral dose of varegacestat.(24 hours)
- The AUC from time 0 extrapolated to infinity, calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant of varegacesatat and AL102-MTB (varegacestat metabolite).(7 days)
- Apparent first-order terminal elimination half-life (t1/2) will be calculated as 0.693/Kel of varegacesatat and AL102-MTB (varegacestat metabolite).(7 days)
- Safety and tolerability of a single oral dose of varegacestat by incidences of treatment-emergent adverse events.(Approximately 56 days)
- Assay sensitivity of the study to detect a small QTc effect using moxifloxacin as a positive control.(24 hours)