Clinical trial NCT06517914: A First-in-Human, Single- and Multiple-Ascending Dose Study of YH35995 in Healthy Adult Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: YH35995
Gaucher Disease
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2024-07-24
Enrollment: 96
Sex: MALE
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: [Part A, B] Treatment-emergent adverse events (TEAEs)
timeFrame: Part A: Day1-150, Part B: To be optimized based on the result of Part A, anticipated 57 days
Secondary outcomes:
measure: [Part A] Maximum observed plasma concentration (Cmax)
timeFrame: Day1-150
measure: [Part A] Time to reach Cmax (Tmax)
timeFrame: Day1-150
measure: [Part A] Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day1-150
measure: [Part A] AUC from time 0 to infinity (AUCinf)
timeFrame: Day1-150
measure: [Part A] Apparent terminal elimination half-life (t1/2)
timeFrame: Day1-150
measure: [Part A] Total plasma clearance (CL/F)
timeFrame: Day1-150
measure: [Part A] Apparent volume of distribution (Vz/F)
timeFrame: Day1-150
measure: [Part B] Cmax during the first dosing interval
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Tmax during the first dosing interval
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] AUC during the first dosing interval (AUCsingle)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] AUC during the dosing interval at steady state (AUCtau,ss)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Cmax at steady state (Cmax,ss)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Tmax at steady state (Tmax,ss)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Accumulation ratio using AUC (Rac(AUC))
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Accumulation ratio using Cmax (Rac(Cmax))
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Plasma concentration at the last observed time point during the dosing interval at steady state (Ctrough)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Average plasma concentration (Cavg)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Clearance at steady state (CLss/F)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Volume of distribution at steady state (Vss)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Effective half-life (t1/2,Rac)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Cerebrospinal fluid to plasma concentration ratio(C/P ratio) of YH35995
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
measure: [Part B] Properly derived PD parameters for YH35995, including the area under the effect curve (AUEC) and maximum effect (Emax)
timeFrame: To be optimized based on the result of Part A, anticipated 57 days
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Bundang-gu
Study officials:
affiliation: CHA Bundang Medical Center
name: Anhye Kim
role: PRINCIPAL_INVESTIGATOR
References: