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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03725072
• Other study ID #: MS200527_0075
• Secondary ID: 2018-003371-35
• Status: Completed
• Phase: Phase 1
• Start date: October 30, 2018
• Est. completion date: December 5, 2018

Study information

• Verified date: July 2020
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 5, 2018
• Est. primary completion date: December 5, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Evobrutinib
Participants will receive a single, oral dose of evobrutinib under fasting conditions as a solution, which will contain [14C]-evobrutinib.

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Radioactivity Recovery Rate of Evobrutinib, Total Radioactivity and its Metabolites		Pre-dose up to Day 35 post-dose
Primary	Percentage Excretion of Evobrutinib, Total Radioactivity and its Metabolites in Urine and Feces		Pre-dose up to Day 35 post-dose
Primary	Renal Clearance of Evobrutinib, Total Radioactivity and its Metabolites		Pre-dose up to Day 35 post-dose
Primary	Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)		Pre-dose up to Day 35 post-dose
Primary	Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)		Pre-dose up to Day 35 post-dose
Primary	Terminal Elimination Half-Life (t1/2) of Total [14C] Radioactivity (Evobrutinib and Metabolites)		Pre-dose up to Day 35 post-dose
Primary	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
Primary	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib		Pre-dose up to Day 35 post-dose
Primary	Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib		Pre-dose up to Day 35 post-dose
Primary	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
Primary	Terminal Elimination Half-Life (t1/2) of Evobrutinib		Pre-dose up to Day 35 post-dose
Primary	Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib		Pre-dose up to Day 35 post-dose
Primary	Apparent Clearance (CL/f) of Evobrutinib		Pre-dose up to Day 35 post-dose
Secondary	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
Secondary	Occurrence of Treatment -emergent Adverse Events (TEAEs) and Serious TEAEs		From time of first dose to end of study participation approximately at Day 37
Secondary	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

External Links

•   Trial Awareness and Transparency website