Clinical trial NCT04880213: Study of M5049 in Healthy Japanese and Caucasian Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
M5049
Japanese
Caucasian
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2021-05-10
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (tlast) (AUC0-tlast) of M5049
timeFrame: 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
measure: Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of M5049
timeFrame: 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
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
timeFrame: Baseline up to Day 8
measure: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters
timeFrame: Baseline up to Day 3
measure: Number of Participants with Clinically Significant Changes from Baseline in Vital Signs
timeFrame: Baseline up to Day 3
measure: Number of Participants with Clinically Significant Changes from Baseline in 12-lead Electrocardiogram (ECGs) Findings
timeFrame: Baseline up to Day 3
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours Post-dose (AUC0-48) of M5049
timeFrame: 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
measure: Time to Reach Maximum Plasma Concentration (tmax) of M5049
timeFrame: 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
measure: Terminal Half-life (t1/2) of M5049
timeFrame: 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
measure: Apparent Total Body Clearance (CL/f) of M5049
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/f) During Terminal Phase of M5049
timeFrame: 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
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit Ltd.
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: