A Randomised, Double-blind, Placebo-controlled Single and Multiple Ascending Dose Study in Healthy Volunteers and Asymptomatic GRN Mutation Carriers to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Change from baseline in vital sign measurement: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg).
研究概览
简要总结
This is a Phase 1, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of VES001 in a two part followed by a multicenter, open-label Phase 1b study in asymptomatic GRN mutation carriers.
Part A will evaluate the safety, tolerability, PK, and PD of single doses of VES001 in healthy volunteers.
Part B will evaluate the safety, tolerability, PK, and PD of multiple doses of VES001 in healthy volunteers.
详细描述
Part A will include six cohorts, with eight participants per cohort. Participants in each cohort will be randomised in a 6:2 ratio (VES001 vs. placebo).
Part B will include three cohorts, with ten participants per cohort. Participants in each cohort will be randomised in a 8:2 ratio (VES001 vs. placebo).
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
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
VES001 (Healthy Participants)
Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers.
干预措施: VES001 (Drug)
Placebo (Healthy Participants)
Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in vital sign measurement: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Incidence of clinically significant abnormalities in safety laboratory values.
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Pulse Rate (bpm).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter Heart Rate (HR).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter beats per minute (bpm)
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter PR Interval
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QRS Interval
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QT Interval.
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QTcB (calculated using Bazzet method).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QTcF, (calculated using Fredericia's method).
时间窗: Part A: 21 weeks. Part B: 13 weeks.
Incidence of clinically significant abnormalities in physical/neurological examination findings.
时间窗: Part A: 21 weeks. Part B: 13 weeks.
次要结局
- Plasma PK parameter: Area under the concentration-time curve from time zero to infinity AUCinf(%extrapolated).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Area under the concentration-time from time zero to time of last measurable concentration (AUClast).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Area under the concentration-time curve from time zero to infinity (AUCinf).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Apparent total clearance following extravascular administration (CL/F).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Maximum concentration (Cmax).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Absorption lag time (tlag).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Time to reach maximum concentration (tmax).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Terminal elimination half-life (t1/2).(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in plasma/CSF ratio in the highest two dose level cohorts in Part A.(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in plasma/CSF ratio in all dose level cohorts in Part B.(Part A: 21 weeks. Part B: 13 weeks.)
- Comparison of the plasma PK of VES001 following a single oral dose in the fed and fasted state in Part A.(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vz/F).(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in CSF in the highest two dose level cohorts in Part A.(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in CSF in all dose level cohorts in Part B.(Part A: 21 weeks. Part B: 13 weeks.)