Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study of M5049 in Healthy Participants

Study Overview
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Brief Summary
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The study will evaluate the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamics (PD), and explore the food effect of M5049 in healthy male and female participants.

Official Title
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A Phase I, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses and Multiple Ascending Doses of M5049 Administered Orally in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: M5049
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight between 50 to 100 kilogram (kg) Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m^2) Other protocol defined inclusion criteria could apply Exclusion Criteria: 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 History of splenectomy History of epilepsy, other neurological disorders, or neuropsychiatric conditions Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: M5049<br> | Drug: M5049<br>* Participants will receive single ascending oral dose of M5049 in Part A. Participants will receive multiple ascending oral dose of M5049 once daily for 14 days or twice daily for 13 days followed by a single dose on Day 14 in the morning in Part B. Participants will receive a single oral dose of M5049 under fed conditions in Part C.<br>|
| Placebo Comparator: Part A: Placebo<br> | Drug: Placebo<br>* Participants will receive placebo matched to M5049.<br>|
| Experimental: Part B: M5049<br> | Drug: M5049<br>* Participants will receive single ascending oral dose of M5049 in Part A. Participants will receive multiple ascending oral dose of M5049 once daily for 14 days or twice daily for 13 days followed by a single dose on Day 14 in the morning in Part B. Participants will receive a single oral dose of M5049 under fed conditions in Part C.<br>|
| Placebo Comparator: Part B: Placebo<br> | Drug: Placebo<br>* Participants will receive placebo matched to M5049.<br>|
| Experimental: Part C: M5049<br> | Drug: M5049<br>* Participants will receive single ascending oral dose of M5049 in Part A. Participants will receive multiple ascending oral dose of M5049 once daily for 14 days or twice daily for 13 days followed by a single dose on Day 14 in the morning in Part B. Participants will receive a single oral dose of M5049 under fed conditions in Part C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) |  | Day 1 up to Day 21 | 
| Part A: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings | Number of participants with clinically significant changes will be reported. | Day 1 up to Day 21 | 
| Part B: Occurrence and Severity of TEAEs and SAEs |  | Day 1 up to Day 33 | 
| Part B: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings | Number of participants with clinically significant changes will be reported. | Day 1 up to Day 33 | 
| Part C: Maximum Observed Plasma Concentration (Cmax) of M5049 |  | Pre-dose up to Day 6 | 
| Part C: Time to Reach Maximum Plasma Concentration (tmax) of M5049 |  | Pre-dose up to Day 6 | 
| Part C: Elimination Rate Constant (λz) of M5049 |  | Pre-dose up to Day 6 | 
| Part C: Apparent Terminal Half-life (t1/2) of M5049 |  | Pre-dose up to Day 6 | 
| Part C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049 |  | Pre-dose up to Day 6 | 
| Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf) |  | Pre-dose up to Day 6 | 
| Part C: Total Body Clearance (CL/f) of M5049 |  | Pre-dose up to Day 6 | 
| Part C: Apparent Volume of Distribution (Vz/f) of M5049 |  | Pre-dose up to Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Maximum Observed Blood Concentration (Cmax) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Time to Reach Maximum Plasma Concentration (tmax) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Elimination Rate Constant (λz) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Apparent Terminal Half-life (t1/2) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf) |  | Pre-dose up to Day 6 | 
| Part A: Total Body Clearance (CL/f) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Apparent Volume of Distribution (Vz/f) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/D) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/D) of M5049 |  | Pre-dose up to Day 6 | 
| Part A: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) on Digital Holter Electrocardiograms (ECG) at Day 2 |  | Baseline, Day 2 | 
| Part A: Time Matched Plasma Concentration of M5049 |  | Pre-dose up to Day 6 | 
| Part B: Maximum Observed Blood Concentration (Cmax) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Elimination Rate Constant (λz) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Apparent Terminal Half-life (t1/2) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf) |  | Pre-dose up to Day 19 | 
| Part B: Total Body Clearance (CL/f) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Apparent Volume of Distribution (Vz/f) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) |  | Pre-dose up to Day 19 | 
| Part B: Accumulation Ratio for Cmax (Racc Cmax) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Accumulation Ratio for AUCtau(Racc AUCtau) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Peak trough Ratio of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Plasma Concentration Prior to the Next Dose (C trough) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Dose Normalized Maximum Observed Plasma Concentration at Steady State (Cmaxss/D) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/D) of M5049 |  | Pre-dose up to Day 19 | 
| Part B: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) on Digital Holter Electrocardiograms (ECG) at Day 2 |  | Baseline, Day 2 | 
| Part B: Time Matched Plasma Concentration of M5049 |  | Pre-dose up to Day 19 | 
| Part C: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) |  | Day 1 up to Day 23 | 
| Part C: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings | Number of participants with clinically significant changes will be reported. | Day 1 up to Day 23 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, M5049