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

Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT03725072
Collaborator
(none)
6
Enrollment
1
Location
1
Arm
1.2
Actual Duration (Months)
5.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Phase I, Open Label, Single Dose Study to Determine the Pharmacokinetics, Metabolism, and Excretion of [14C]-Evobrutinib in Healthy Participants
Actual Study Start Date :
Oct 30, 2018
Actual Primary Completion Date :
Dec 5, 2018
Actual Study Completion Date :
Dec 5, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Evobrutinib

Drug: Evobrutinib
Participants will receive a single, oral dose of evobrutinib under fasting conditions as a solution, which will contain [14C]-evobrutinib.
Other Names:
  • M2951

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Total Radioactivity Recovery Rate of Evobrutinib, Total Radioactivity and its Metabolites [Pre-dose up to Day 35 post-dose]

    2. Percentage Excretion of Evobrutinib, Total Radioactivity and its Metabolites in Urine and Feces [Pre-dose up to Day 35 post-dose]

    3. Renal Clearance of Evobrutinib, Total Radioactivity and its Metabolites [Pre-dose up to Day 35 post-dose]

    4. Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites) [Pre-dose up to Day 35 post-dose]

    5. Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites) [Pre-dose up to Day 35 post-dose]

    6. Terminal Elimination Half-Life (t1/2) of Total [14C] Radioactivity (Evobrutinib and Metabolites) [Pre-dose up to Day 35 post-dose]

    7. 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]

    8. Maximum Observed Plasma Concentration (Cmax) of Evobrutinib [Pre-dose up to Day 35 post-dose]

    9. Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib [Pre-dose up to Day 35 post-dose]

    10. 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]

    11. Terminal Elimination Half-Life (t1/2) of Evobrutinib [Pre-dose up to Day 35 post-dose]

    12. Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib [Pre-dose up to Day 35 post-dose]

    13. Apparent Clearance (CL/f) of Evobrutinib [Pre-dose up to Day 35 post-dose]

    Secondary Outcome Measures

    1. 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.

    2. Occurrence of Treatment -emergent Adverse Events (TEAEs) and Serious TEAEs [From time of first dose to end of study participation approximately at Day 37]

    3. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    Male
    Accepts 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 exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 PRA Health Sciences Groningen Netherlands 9728 NZ

    Sponsors and Collaborators

    • Merck KGaA, Darmstadt, Germany

    Investigators

    • Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT03725072
    Other Study ID Numbers:
    • MS200527_0075
    • 2018-003371-35
    First Posted:
    Oct 30, 2018
    Last Update Posted:
    Jul 7, 2020
    Last Verified:
    Jul 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck KGaA, Darmstadt, Germany
    [14C]-evobrutinib
    Healthy
    Pharmacokinetics
    Metabolism
    Excretion

    Study Results

    No Results Posted as of Jul 7, 2020