Healthy
Conditions
Keywords
Pharmacokinetics, M5049
Brief summary
The study will evaluate the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamics (PD), and explore the food effect of M5049 in healthy male and female participants.
Interventions
DRUGM5049
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.
DRUGPlacebo
Participants will receive placebo matched to M5049.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 | Day 1 up to Day 21 | Number of participants with clinically significant changes will be reported. |
| 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 | Day 1 up to Day 33 | Number of participants with clinically significant changes will be reported. |
| 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: 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: Apparent Volume of Distribution (Vz/f) 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 | Day 1 up to Day 23 | Number of participants with clinically significant changes will be reported. |
| 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: 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 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 | — |
Countries
Germany
Outcome results
None listed