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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Evobrutinib

• Registration Number: NCT03725072
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-29
• Study First Submitted QC: 2018-10-29
• Study Start: 2018-10-30
• Study First Posted: 2018-10-30
• Primary Completion: 2018-12-05
• Study Completion: 2018-12-05
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-03
• Last Update Posted: 2020-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Evobrutinib	Evobrutinib	-

Primary Outcome Measures

Name	Time	Method
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
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
Terminal Elimination Half-Life (t1/2) of Evobrutinib	Pre-dose up to Day 35 post-dose
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
Maximum Observed Plasma Concentration (Cmax) 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
Time to Reach Maximum Plasma Concentration (Tmax) 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
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

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings	From time of first dose to end of study participation approximately at Day 37	Number of participants with clinically significant abnormalities will be reported.
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

Trial Locations

Locations (1)

PRA Health Sciences; 🇳🇱 Groningen, Netherlands