A First-in-Human, Single- and Multiple-Ascending Dose Study of YH35995 in Healthy Adult Male Participants
- Registration Number
- NCT06517914
- Lead Sponsor
- Yuhan Corporation
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 96
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description YH35995 YH35995 \[Part A\] Participants will be orally administered a single dose of YH35995 in six 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). Placebo Placebo \[Part A\] Participants will be orally administered a single dose of Placebo in six 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).
- Primary Outcome Measures
Name Time Method [Part A, B] Treatment-emergent adverse events (TEAEs) Part A: Day1-150, Part B: To be optimized based on the result of Part A, anticipated 57 days To assess the safety and tolerability of a single dose and multiple dose administration of YH35995
- Secondary Outcome Measures
Name Time Method [Part B] Volume of distribution at steady state (Vss) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Effective half-life (t1/2,Rac) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Cerebrospinal fluid to plasma concentration ratio(C/P ratio) of YH35995 To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part A] Time to reach Cmax (Tmax) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part A] Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part A] AUC from time 0 to infinity (AUCinf) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part A] Apparent terminal elimination half-life (t1/2) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part A] Total plasma clearance (CL/F) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part A] Maximum observed plasma concentration (Cmax) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part B] AUC during the first dosing interval (AUCsingle) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part A] Apparent volume of distribution (Vz/F) Day1-150 To characterize the pharmacokinetics (PK) of YH35995
[Part B] Cmax during the first dosing interval To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Tmax during the first dosing interval To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] AUC during the dosing interval at steady state (AUCtau,ss) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Cmax at steady state (Cmax,ss) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Tmax at steady state (Tmax,ss) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Accumulation ratio using AUC (Rac(AUC)) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Accumulation ratio using Cmax (Rac(Cmax)) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Plasma concentration at the last observed time point during the dosing interval at steady state (Ctrough) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Average plasma concentration (Cavg) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Clearance at steady state (CLss/F) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacokinetics (PK) of YH35995 after multiple dose administration
[Part B] Properly derived PD parameters for YH35995, including the area under the effect curve (AUEC) and maximum effect (Emax) To be optimized based on the result of Part A, anticipated 57 days To assess the pharmacodynamics (PD) of YH35995 after multiple dose administration
Trial Locations
- Locations (1)
CHA Bundang Medical Center
🇰🇷Seongnam, Bundang-gu, Korea, Republic of