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Completed

NCT Number: NCT03725072

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

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

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

PRA Health Sciences

Groningen, 9728 NZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Evobrutinib

Drug

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

Other names: M2951

Primary outcomes

  1. Total Radioactivity Recovery Rate of Evobrutinib, Total Radioactivity and its Metabolites

    Time frame: Pre-dose up to Day 35 post-dose

  2. Percentage Excretion of Evobrutinib, Total Radioactivity and its Metabolites in Urine and Feces

    Time frame: Pre-dose up to Day 35 post-dose

  3. Renal Clearance of Evobrutinib, Total Radioactivity and its Metabolites

    Time frame: Pre-dose up to Day 35 post-dose

  4. Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)

    Time frame: Pre-dose up to Day 35 post-dose

  5. Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity (Evobrutinib and Metabolites)

    Time frame: Pre-dose up to Day 35 post-dose

  6. Terminal Elimination Half-Life (t1/2) of Total [14C] Radioactivity (Evobrutinib and Metabolites)

    Time frame: 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)

    Time frame: Pre-dose up to Day 35 post-dose

  8. Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

    Time frame: Pre-dose up to Day 35 post-dose

  9. Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib

    Time frame: 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

    Time frame: Pre-dose up to Day 35 post-dose

  11. Terminal Elimination Half-Life (t1/2) of Evobrutinib

    Time frame: Pre-dose up to Day 35 post-dose

  12. Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib

    Time frame: Pre-dose up to Day 35 post-dose

  13. Apparent Clearance (CL/f) of Evobrutinib

    Time frame: Pre-dose up to Day 35 post-dose

Secondary outcomes

  1. Number of Participants with Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings

    Time frame: 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

    Time frame: 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

    Time frame: From time of first dose to end of study participation approximately at Day 37

Sponsors and collaborators

Lead sponsor

Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Oct 30, 2018
Registry last updated
Jul 7, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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