An Open-label Study to Characterize the Pharmacokinetics, Safety and Tolerability of Single and Multiple Oral Doses of MK-4482 in Chinese Healthy Male Participants
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Elimination Half Life (T1/2) After Single Oral Dose of MK-4482 in Period 1
Study Overview
Brief Summary
The goal of the study is to learn what happens to MK-4482 after single and multiple doses in healthy Chinese participants over time. Researchers also want to learn about the safety of MK-4482, including how well people tolerate it.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •The main inclusion criteria include but are not limited to the following:
- •- Has a Body Mass Index (BMI) of 19 to 24 weight (kg)/height (m)2, inclusive, and body weight of ≥ 50 kg at the screening visit.
Exclusion Criteria
- •The main exclusion criteria include but are not limited to the following:
- •Has a history of clinically significant abnormalities or diseases.
- •Has history of cancer.
- •Has a history of significant multiple and/or severe allergies.
- •Had any major surgery.
- •Has participated in another investigational study within 3 months prior to the screening visit.
Arms & Interventions
MK-4482
Participants in period 1 received, MK-4482 800 mg single oral dose in the morning on Day 1. Participants in period 2 received, MK-4482 800mg oral dose administered every 12 hours (Q12H) on Day 1 through Day 6 for11 doses.
Intervention: MK-4482 (Drug)
Outcomes
Primary Outcomes
Elimination Half Life (T1/2) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
T1/2 is defined as the time required for the concentration or amount of NHC in the body to be reduced by one-half after a single oral dose of MK-4482 in period 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax ) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
Tmax of NHC following multiple oral doses of MK-4482 in period 2.
The Minimum Concentration (Ctrough) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
Ctrough of NHC that occurred following multiple doses of MK-4482 in period 2.
Apparent Volume of Distribution (Vz/F) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
Vz/F of NHC during terminal phase after single oral dose of MK-4482 in period 1.
Apparent Total Clearance (CL/F) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
CL/F of NHC from plasma after single oral dose of MK-4482 in period 1.
The Maximum Observed Plasma Concentration (Cmax) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
Cmax of N-hydroxycytidine (NHC) after a single oral dose of MK-4482 in period 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax ) After Single Oral Dose of MK-4482 in Period 1.
Time Frame: At designated time points up to 72 hours post-dose
Tmax of NHC following single oral dose of MK-4482 in period 1.
Apparent Volume of Distribution (Vz/F) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
Vz/F of NHC during terminal phase after multiple doses of MK-4482 in period 2.
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC0-12hr) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
This is a measure of the average amount of NHC in the plasma over a period of 12 hours after single oral dose of MK-4482 in period 1.
Elimination Half Life (T1/2) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
T1/2 is defined as the time required for the concentration or amount of NHC in the body to be reduced by one-half after multiple oral doses of MK-4482 in period 2.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC0-last) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
AUC0-last of NHC following a single oral dose of MK-4482 in period 1.
Area Under The Plasma Concentration Versus Time Curve From Time Zero (pre-dose) to Extrapolated Infinite Time (AUC0-inf) After Single Oral Dose of MK-4482 in Period 1
Time Frame: At designated time points up to 72 hours post-dose
AUC0-inf of NHC after single oral dose of MK-4482 in period 1.
The Maximum Observed Plasma Concentration (Cmax) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
Cmax of NHC after multiple oral doses of MK-4482 in period 2.
Clearance at Steady State (CLss/F) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
CLss/F of plasma NHC following multiple doses of MK-4482 in period 2.
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC0-12hr) After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
This is a measure of the average amount of NHC in the plasma over a period of 12 hours after multiple oral doses of MK-4482 in period 2.
Accumulation Ratio on Cmax After Multiple Oral Doses of MK-4482 in Period 2
Time Frame: At designated time points up to 72 hours post-dose
The maximum concentration at steady state following multiple doses of MK-4482 in period 2 divided by the maximum concentration following the initial dosing in Period 1.
Accumulation Ratio on AUC0-12hr After Multiple Oral Doses of MK-4482
Time Frame: At designated time points up to 72 hours post-dose
The AUC0-12hr at steady state following multiple doses of MK-4482 in period 2 divided by the AUC0-12hr following the initial dosing in Period 1.
Secondary Outcomes
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to ~ 5.5 weeks)
- Number of Participants Who Experience an Adverse Event (AE)(Up to ~ 5.5 weeks)