Study of M5049 in Healthy Japanese and Caucasian Participants

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: M5049
* Drug: M5049
* Drug: M5049


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, M5049, Japanese, Caucasian