Human Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]-Evobrutinib

Phase I, Open Label, Single Dose Study to Determine the Pharmacokinetics, Metabolism, and Excretion of [14C]-Evobrutinib in Healthy Participants

The purpose of the study is to determine the absorption, metabolism, and excretion of [14C]-evobrutinib in healthy participants

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Evobrutinib

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Participants are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring
• Have a body weight within 50.0 to 120.0 kilogram (kg) (inclusive) and body mass index within the range 19.0 - 30.0 kilogram per meter square (kg/m^2) (inclusive)
• Male participants agree to be consistent with local regulations on contraception methods
• Can give signed informed consent
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders
• Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery
• Any surgical or medical condition which might significantly alter the ADME of drugs
• History of any malignancy, chronic or recurrent acute infection
• History of shingles
• History of drug hypersensitivity ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients
• History of alcoholism or drug abuse
• History of residential exposure to tuberculosis, or a positive QuantiFERON test at screening
• Administration of live vaccines or live-attenuated virus vaccines
• Any condition, including findings in the laboratory tests, medical history, or other screening assessments, that in the opinion of the Investigator constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study's objectives, conduct, or evaluation
• Prior/concomitant therapy
• Relevant radiation exposure
• Clinically relevant findings (excluding minor deviations) in biochemistry, hematology, coagulation and urinalysis
• Vital signs (pulse rate and blood pressure) outside the normal range
• Estimated Glomerular Filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
• Semi supine systolic blood pressure (SBP) greater than (>) 140 millimeters of Mercury (mmHg) or less than (<) 90 mmHg, diastolic blood pressure (DBP) > 90 mmHg or < 45 mmHg and pulse rate >= 100 bpm or =< 40 bpm, at admission
• 12-Lead electrocardiogram (ECG) showing a QTcF > 450 millisecond (ms), PR > 215 ms, or QRS > 120 ms
• Positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody, hepatitis C antibody, or human immunodeficiency virus (HIV) I and II tests at screening
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evobrutinib	Drug: Evobrutinib; Participants will receive a single, oral dose of evobrutinib under fasting conditions as a solution, which will contain [14C]-evobrutinib.; Other Names: M2951

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Radioactivity Recovery Rate of Evobrutinib, Total Radioactivity and its Metabolites	Pre-dose up to Day 35 post-dose
Percentage Excretion of Evobrutinib, Total Radioactivity and its Metabolites in Urine and Feces	Pre-dose up to Day 35 post-dose
Renal Clearance of Evobrutinib, Total Radioactivity and its Metabolites	Pre-dose up to Day 35 post-dose
Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)	Pre-dose up to Day 35 post-dose
Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)	Pre-dose up to Day 35 post-dose
Terminal Elimination Half-Life (t1/2) of Total [14C] Radioactivity (Evobrutinib and Metabolites)	Pre-dose up to Day 35 post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Total [14C] Radioactivity (Evobrutinib and Metabolites)	Pre-dose up to Day 35 post-dose
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	Pre-dose up to Day 35 post-dose
Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib	Pre-dose up to Day 35 post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Evobrutinib	Pre-dose up to Day 35 post-dose
Terminal Elimination Half-Life (t1/2) of Evobrutinib	Pre-dose up to Day 35 post-dose
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib	Pre-dose up to Day 35 post-dose
Apparent Clearance (CL/f) of Evobrutinib	Pre-dose up to Day 35 post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings	Number of participants with clinically significant abnormalities will be reported.	From time of first dose to end of study participation approximately at Day 37
Occurrence of Treatment -emergent Adverse Events (TEAEs) and Serious TEAEs		From time of first dose to end of study participation approximately at Day 37
Occurrence of Treatment -emergent Adverse Events (TEAEs) and Serious TEAEs by Severity		From time of first dose to end of study participation approximately at Day 37

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): December 5, 2018

Study Registration Dates

• First Submitted: October 29, 2018
• First Submitted That Met QC Criteria: October 29, 2018
• First Posted (Actual): October 30, 2018

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 3, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Metabolism; Excretion; [14C]-evobrutinib
• Other Study ID Numbers: MS200527_0075; 2018-003371-35 (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