Study of M5049 in Healthy Japanese and Caucasian Participants

A Phase I, Open-label, Single-dose, Sequential Dose Group Study of Orally Administered M5049 Tablet Formulation in Healthy Japanese and Caucasian Participants to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

The purpose of this study is to evaluate and determine the safety, tolerability and pharmacokinetics of single-doses of M5049 up to 3 dose levels administered as film-coated tablet under fasted conditions in healthy Japanese and Caucasian participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: M5049; Drug: M5049; Drug: M5049

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • Covance Clinical Research Unit Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Japanese participants must be first generation (born in Japan) with both biological parents and all 4 biological grandparents being Japanese native born. Caucasian participants must have both biological parents and 4 biological grandparents of Caucasian descent
• Overtly healthy participants as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring (blood pressure, heart rate and 12-Lead resting ECG)
• Participants with body weight within 45 to 90 kilograms (kg) (female) and 55 to 90 kg (male) and body mass index (BMI) between 18.5 and 29.9 kilograms per meter square (kg/m^2)
• A Caucasian participant will be matched by body weight (± 20% body weight [kg]), height (± 15% height [centimeter (cm) ]) and sex to each Japanese participant
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants with history of clinically relevant disease of any organ system that may interfere with the objectives of the study or provide a risk to the health of the participant
• Participants with history of relevant drug hypersensitivity
• Participants with history of splenectomy, epilepsy, other neurological disorders or neuropsychiatric conditions
• Participants with history of a tuberculosis and positive Screening test for hepatitis B surface antigen
• Participants with history of alcoholism or drug abuse
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Japanese: M5049 Dose A (low dose)	Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at low dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at medium dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at high dose on Day 1 under fasted condition.
Experimental: Japanese: M5049 Dose B (medium dose)	Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at low dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at medium dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at high dose on Day 1 under fasted condition.
Experimental: Japanese: M5049 Dose C (high dose)	Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at low dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at medium dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at high dose on Day 1 under fasted condition.
Experimental: Caucasian: M5049 Dose A (low dose)	Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at low dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at medium dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at high dose on Day 1 under fasted condition.
Experimental: Caucasian: M5049 Dose B (medium dose)	Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at low dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at medium dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at high dose on Day 1 under fasted condition.
Experimental: Caucasian: M5049 Dose C (high dose)	Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at low dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at medium dose on Day 1 under fasted condition.; Drug: M5049; Participants will receive single oral dose of film-coated tablet M5049 at high dose on Day 1 under fasted condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (tlast) (AUC0-tlast) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death	Baseline up to Day 8
Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters	Baseline up to Day 3
Number of Participants with Clinically Significant Changes from Baseline in Vital Signs	Baseline up to Day 3
Number of Participants with Clinically Significant Changes from Baseline in 12-lead Electrocardiogram (ECGs) Findings	Baseline up to Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours Post-dose (AUC0-48) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Time to Reach Maximum Plasma Concentration (tmax) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Terminal Half-life (t1/2) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Apparent Total Body Clearance (CL/f) of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
Apparent Volume of Distribution (Vz/f) During Terminal Phase of M5049	Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): November 23, 2021
• Study Completion (Actual): November 23, 2021

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Healthy; Japanese; Caucasian; M5049
• Other Study ID Numbers: MS200569_0005; 2020-005408-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No