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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03676322
• Other study ID #: MS200569_0001
• Secondary ID: 2018-001256-35
• Status: Completed
• Phase: Phase 1
• Start date: September 20, 2018
• Est. completion date: July 26, 2019

Study information

• Verified date: November 2019
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: July 26, 2019
• Est. primary completion date: July 26, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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
Participants will receive placebo matched to M5049.

Locations

Country	Name	City	State
Germany	Nuvisan GmbH	Neu-Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)		Day 1 up to Day 21
Primary	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
Primary	Part B: Occurrence and Severity of TEAEs and SAEs		Day 1 up to Day 33
Primary	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
Primary	Part C: Maximum Observed Plasma Concentration (Cmax) of M5049		Pre-dose up to Day 6
Primary	Part C: Time to Reach Maximum Plasma Concentration (tmax) of M5049		Pre-dose up to Day 6
Primary	Part C: Elimination Rate Constant (?z) of M5049		Pre-dose up to Day 6
Primary	Part C: Apparent Terminal Half-life (t1/2) of M5049		Pre-dose up to Day 6
Primary	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
Primary	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
Primary	Part C: Total Body Clearance (CL/f) of M5049		Pre-dose up to Day 6
Primary	Part C: Apparent Volume of Distribution (Vz/f) of M5049		Pre-dose up to Day 6
Secondary	Part A: Maximum Observed Blood Concentration (Cmax) of M5049		Pre-dose up to Day 6
Secondary	Part A: Time to Reach Maximum Plasma Concentration (tmax) of M5049		Pre-dose up to Day 6
Secondary	Part A: Elimination Rate Constant (?z) of M5049		Pre-dose up to Day 6
Secondary	Part A: Apparent Terminal Half-life (t1/2) of M5049		Pre-dose up to Day 6
Secondary	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
Secondary	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
Secondary	Part A: Total Body Clearance (CL/f) of M5049		Pre-dose up to Day 6
Secondary	Part A: Apparent Volume of Distribution (Vz/f) of M5049		Pre-dose up to Day 6
Secondary	Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/D) of M5049		Pre-dose up to Day 6
Secondary	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
Secondary	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
Secondary	Part A: Time Matched Plasma Concentration of M5049		Pre-dose up to Day 6
Secondary	Part B: Maximum Observed Blood Concentration (Cmax) of M5049		Pre-dose up to Day 19
Secondary	Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049		Pre-dose up to Day 19
Secondary	Part B: Elimination Rate Constant (?z) of M5049		Pre-dose up to Day 19
Secondary	Part B: Apparent Terminal Half-life (t1/2) of M5049		Pre-dose up to Day 19
Secondary	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
Secondary	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
Secondary	Part B: Total Body Clearance (CL/f) of M5049		Pre-dose up to Day 19
Secondary	Part B: Apparent Volume of Distribution (Vz/f) of M5049		Pre-dose up to Day 19
Secondary	Part B: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau)		Pre-dose up to Day 19
Secondary	Part B: Accumulation Ratio for Cmax (Racc Cmax) of M5049		Pre-dose up to Day 19
Secondary	Part B: Accumulation Ratio for AUCtau(Racc AUCtau) of M5049		Pre-dose up to Day 19
Secondary	Part B: Peak trough Ratio of M5049		Pre-dose up to Day 19
Secondary	Part B: Plasma Concentration Prior to the Next Dose (C trough) of M5049		Pre-dose up to Day 19
Secondary	Part B: Dose Normalized Maximum Observed Plasma Concentration at Steady State (Cmaxss/D) of M5049		Pre-dose up to Day 19
Secondary	Part B: Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/D) of M5049		Pre-dose up to Day 19
Secondary	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
Secondary	Part B: Time Matched Plasma Concentration of M5049		Pre-dose up to Day 19
Secondary	Part C: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)		Day 1 up to Day 23
Secondary	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