Clinical trial NCT03676322: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study of M5049 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Pharmacokinetics
M5049
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-09-18
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
timeFrame: Day 1 up to Day 21
measure: Part A: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Day 1 up to Day 21
measure: Part B: Occurrence and Severity of TEAEs and SAEs
timeFrame: Day 1 up to Day 33
measure: Part B: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Day 1 up to Day 33
measure: Part C: Maximum Observed Plasma Concentration (Cmax) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part C: Time to Reach Maximum Plasma Concentration (tmax) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part C: Elimination Rate Constant (λz) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part C: Apparent Terminal Half-life (t1/2) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf)
timeFrame: Pre-dose up to Day 6
measure: Part C: Total Body Clearance (CL/f) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part C: Apparent Volume of Distribution (Vz/f) of M5049
timeFrame: Pre-dose up to Day 6
Secondary outcomes:
measure: Part A: Maximum Observed Blood Concentration (Cmax) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Time to Reach Maximum Plasma Concentration (tmax) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Elimination Rate Constant (λz) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Apparent Terminal Half-life (t1/2) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf)
timeFrame: Pre-dose up to Day 6
measure: Part A: Total Body Clearance (CL/f) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Apparent Volume of Distribution (Vz/f) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/D) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/D) of M5049
timeFrame: Pre-dose up to Day 6
measure: Part A: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) on Digital Holter Electrocardiograms (ECG) at Day 2
timeFrame: Baseline, Day 2
measure: Part A: Time Matched Plasma Concentration of M5049
timeFrame: Pre-dose up to Day 6
measure: Part B: Maximum Observed Blood Concentration (Cmax) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Elimination Rate Constant (λz) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Apparent Terminal Half-life (t1/2) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf)
timeFrame: Pre-dose up to Day 19
measure: Part B: Total Body Clearance (CL/f) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Apparent Volume of Distribution (Vz/f) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau)
timeFrame: Pre-dose up to Day 19
measure: Part B: Accumulation Ratio for Cmax (Racc Cmax) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Accumulation Ratio for AUCtau(Racc AUCtau) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Peak trough Ratio of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Plasma Concentration Prior to the Next Dose (C trough) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Dose Normalized Maximum Observed Plasma Concentration at Steady State (Cmaxss/D) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/D) of M5049
timeFrame: Pre-dose up to Day 19
measure: Part B: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) on Digital Holter Electrocardiograms (ECG) at Day 2
timeFrame: Baseline, Day 2
measure: Part B: Time Matched Plasma Concentration of M5049
timeFrame: Pre-dose up to Day 19
measure: Part C: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
timeFrame: Day 1 up to Day 23
measure: Part C: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Day 1 up to Day 23
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: