Healthy
Conditions
Keywords
[14C]-evobrutinib, Healthy, Pharmacokinetics, Metabolism, Excretion
Brief summary
The purpose of the study is to determine the absorption, metabolism, and excretion of \[14C\]-evobrutinib in healthy participants
Interventions
DRUGEvobrutinib
Participants will receive a single, oral dose of evobrutinib under fasting conditions as a solution, which will contain \[14C\]-evobrutinib.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Apparent Clearance (CL/f) 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 |
| Renal Clearance of Evobrutinib, Total Radioactivity and its Metabolites | 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
Countries
Netherlands
Outcome results
None listed