A First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following Oral Administration of YH35995 in Healthy Adult Male Participants
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 94
- 试验地点
- 2
- 主要终点
- [Part A, B] Treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a randomized, double-blind, first-in-human study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of YH35995
详细描述
YH35995 is being developed as a treatment for the neurological symptoms of Gaucher Disease type 3. This study is a first-in-human (FIH), phase 1, randomized, double-blind, placebo-controlled study of YH35995, which consists of two parts. In Part A (SAD), single ascending dose of YH35995 is administered to healthy male participants to assess its safety, tolerability, PK, and PD. In Part B (MAD), multiple ascending dose of YH35995 is administered to healthy male participants to assess its safety, tolerability, PK, and PD.
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)
盲法说明
This is a double-blind study, meaning that YH35995 tablets and placebo tablets will be identical in appearance and will be packaged in the same way.
Information about the treatment arm to which participants are assigned must remain blinded for the duration of the study unless information about the causal relationship between the adverse event and the Investigational Product that meets the drug withdrawal criteria becomes essential or, in an emergency, if the information about the Investigational Product becomes critical for treating the participant.
入排标准
- 年龄范围
- 19 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male between the ages of 19 and 45 at the time of providing written consent
- •Participants who weigh at least 50 kg at screening and have a body mass index (BMI) of at least 18.0 kg/m2 and less than 30 kg/m2
- •Participants who have been fully informed about and fully understand this study, have voluntarily decided to participate, and have agreed in writing to comply with the guidelines of the study during the duration of the study
排除标准
- •Participation in a bioequivalence trial or any other clinical trials within 6 months prior to the first scheduled dose of the IP (within 1 month of the first scheduled dose for participants who have taken part in a dietary supplement clinical trial)
- •Individuals with clinically significant abnormal results that do not match any other inclusion/exclusion criteria, as determined by the principal investigator and the delegated persons(investigator)
- •Individuals who are unwilling or unable to comply with the participant guidelines described in this protocol
研究组 & 干预措施
YH35995
[Part A] Participants will be orally administered a single dose of YH35995 in five dose groups, gradually escalating from lower to higher doses. Each cohort includes 10 participants (8 randomly assigned to the YH35995 arm and 2 randomly assigned to the placebo arm).
[Part B] Participants will receive multiple oral doses of YH35995 once every 4 weeks in three dose groups. Each cohort includes 12 participants (9 randomly assigned to the YH35995 arm and 3 randomly assigned to the placebo arm).
干预措施: YH35995 (Drug)
Placebo
[Part A] Participants will be orally administered a single dose of Placebo in five dose groups, gradually escalating from lower to higher doses. Each cohort includes 10 participants (8 randomly assigned to the YH35995 arm and 2 randomly assigned to the placebo arm).
[Part B] Participants will receive multiple oral doses of Placebo once every 4 weeks in three dose groups. Each cohort includes 12 participants (9 randomly assigned to the YH35995 arm and 3 randomly assigned to the placebo arm).
干预措施: Placebo (Drug)
结局指标
主要结局
[Part A, B] Treatment-emergent adverse events (TEAEs)
时间窗: Part A: Day1-150, Part B: Day1-232
To assess the safety and tolerability of a single dose and multiple dose administration of YH35995
次要结局
- [Part A] Maximum observed plasma concentration (Cmax)(Day1-150)
- [Part A] Time to reach Cmax (Tmax)(Day1-150)
- [Part A] Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)(Day1-150)
- [Part A] AUC from time 0 to infinity (AUCinf)(Day1-150)
- [Part A] Apparent terminal elimination half-life (t1/2)(Day1-150)
- [Part A] Total plasma clearance (CL/F)(Day1-150)
- [Part A] Apparent volume of distribution (Vz/F)(Day1-150)
- [Part A] Maximum observed plasma concentration (Cmax)(Day1-150)
- [Part A] Time to reach Cmax (Tmax)(Day1-150)
- [Part A] Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)(Day1-150)
- [Part A] AUC from time 0 to infinity (AUCinf)(Day1-150)
- [Part A] Apparent terminal elimination half-life (t1/2)(Day1-150)
- [Part A] Total plasma clearance (CL/F)(Day1-150)
- [Part A] Apparent volume of distribution (Vz/F)(Day1-150)
- [Part B] Cmax during the first dosing interval(Day1-232)
- [Part B] Tmax during the first dosing interval(Day1-232)
- [Part B] AUC during the first dosing interval (AUCsingle)(Day1-232)
- [Part B] AUC during the dosing interval at steady state (AUCtau,ss)(Day1-232)
- [Part B] Cmax at steady state (Cmax,ss)(Day1-232)
- [Part B] Tmax at steady state (Tmax,ss)(Day1-232)
- [Part B] Accumulation ratio using AUC (Rac(AUC))(Day1-232)
- [Part B] Accumulation ratio using Cmax (Rac(Cmax))(Day1-232)
- [Part B] Plasma concentration at the last observed time point during the dosing interval at steady state (Ctrough)(Day1-232)
- [Part B] Average plasma concentration (Cavg)(Day1-232)
- [Part B] Clearance at steady state (CLss/F)(Day1-232)
- [Part B] Volume of distribution at steady state (Vss)(Day1-232)
- [Part B] Effective half-life (t1/2,Rac)(Day1-232)
- [Part B] Cerebrospinal fluid to plasma concentration ratio(C/P ratio) of YH35995(Day1-232)
- [Part B] Properly derived PD parameters for YH35995, including the area under the effect curve (AUEC) and maximum effect (Emax)(Day1-232)