Clinical trial NCT03725072: Human Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]-Evobrutinib
Official title: Phase I, Open Label, Single Dose Study to Determine the Pharmacokinetics, Metabolism, and Excretion of [14C]-Evobrutinib in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: [14C]-evobrutinib
Healthy
Pharmacokinetics
Metabolism
Excretion
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-10-30
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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


Eligibility criteria: 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

Primary outcomes:
measure: Total Radioactivity Recovery Rate of Evobrutinib, Total Radioactivity and its Metabolites
timeFrame: Pre-dose up to Day 35 post-dose
measure: Percentage Excretion of Evobrutinib, Total Radioactivity and its Metabolites in Urine and Feces
timeFrame: Pre-dose up to Day 35 post-dose
measure: Renal Clearance of Evobrutinib, Total Radioactivity and its Metabolites
timeFrame: Pre-dose up to Day 35 post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)
timeFrame: Pre-dose up to Day 35 post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)
timeFrame: Pre-dose up to Day 35 post-dose
measure: Terminal Elimination Half-Life (t1/2) of Total [14C] Radioactivity (Evobrutinib and Metabolites)
timeFrame: Pre-dose up to Day 35 post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Total [14C] Radioactivity (Evobrutinib and Metabolites)
timeFrame: Pre-dose up to Day 35 post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
timeFrame: Pre-dose up to Day 35 post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib
timeFrame: Pre-dose up to Day 35 post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Evobrutinib
timeFrame: Pre-dose up to Day 35 post-dose
measure: Terminal Elimination Half-Life (t1/2) of Evobrutinib
timeFrame: Pre-dose up to Day 35 post-dose
measure: Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib
timeFrame: Pre-dose up to Day 35 post-dose
measure: Apparent Clearance (CL/f) of Evobrutinib
timeFrame: Pre-dose up to Day 35 post-dose
Secondary outcomes:
measure: Number of Participants with Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings
timeFrame: From time of first dose to end of study participation approximately at Day 37
measure: Occurrence of Treatment -emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From time of first dose to end of study participation approximately at Day 37
measure: Occurrence of Treatment -emergent Adverse Events (TEAEs) and Serious TEAEs by Severity
timeFrame: From time of first dose to end of study participation approximately at Day 37
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Health Sciences
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: