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

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

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Evobrutinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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[14C]-evobrutinib, Healthy, Pharmacokinetics, Metabolism, Excretion