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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: M5049

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany, 89231
    • Nuvisan GmBH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Part A: Placebo	Drug: Placebo; Participants will receive placebo matched to M5049.
EXPERIMENTAL: Part A: M5049	Drug: M5049; 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.
EXPERIMENTAL: Part B: M5049	Drug: M5049; 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.
PLACEBO_COMPARATOR: Part B: Placebo	Drug: Placebo; Participants will receive placebo matched to M5049.
EXPERIMENTAL: Part C: M5049	Drug: M5049; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 20, 2018
• Primary Completion (ACTUAL): July 26, 2019
• Study Completion (ACTUAL): July 26, 2019

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (ACTUAL): September 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 2, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; M5049
• Other Study ID Numbers: MS200569_0001; 2018-001256-35 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No