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OpenTrials
Completed

NCT Number: NCT03436394

Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)

The study will investigate the PK and safety of evobrutinib in subjects with different degree of renal impairment as compared to subjects with normal renal function.

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Key information

Age range

18 year–79 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Please Contact the Merck KGaA Communication Center

Darmstadt, 64293, Germany

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Male and Female subjects with total body weight between 50.0 and 100.0 kilograms(kg) (inclusive) and body mass index (BMI) between 19.0 and 36.0 kg per meter square (inclusive) at the time of the screening examination
  • For subjects with impaired renal function: Subjects must have an eGFR according to the Modification of diet in renal disease (MDRD) equation of less than 90 mL per minute at screening and the possibility of stratification to one of the groups and a stable renal function as defined by either: if the time interval between screening and dosing is greater than 10 days, two eGFR with the second estimate within 20% of prior value or historical records of stable function over the past 3 months if within 20 percentage of screening value and within 10 days of dosing
  • Other protocol defined inclusion criteria could apply

Exclusion criteria

  • History or presence of respiratory, gastrointestinal (including bariatric or other gastric surgeries, or other conditions that may affect drug absorption) hepatic (including hepatorenal syndrome), hematological, lymphatic, neurological (including seizures), cardiovascular (including ventricular dysfunction and congestive heart failure), psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders that may affect the safety of the subject.
  • Clinical history of any autoimmune disorder
  • Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening, which might interfere with the objectives of the study or the study procedures
  • History of any malignancy except superficial basal cell carcinoma treated for curative intent may be allowed
  • Other protocol defined exclusion criteria could apply

Treatment and study plan

Evobrutinib

Drug

Subjects will be administered a single oral dose of evobrutinib under fasting conditions.

Other names: MSC2364447C, M2951

Primary outcomes

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

  2. Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

  3. Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

Secondary outcomes

  1. Occurrences of Treatment-emergent Adverse Events (TEAEs)

    Time frame: Day 1 up to Day 6

  2. Number of Subjects With TEAEs According to Severity

    Time frame: Day 1 up to Day 6

  3. Number of Subjects With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings

    Time frame: Day 1 up to Day 6

    Number of subjects with clinically significant abnormalities will be reported.

  4. Time to Reach the Maximum Plasma Concentration (tmax) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

  5. Time Prior to the First Measurable (Non-Zero) Concentration (t lag) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

  6. Terminal Rate Constant (λz) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

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

    Time frame: Pre-dose up to 30 hours post-dose

  8. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours After Dosing (AUC 0-24h) of Evobrutinib

    Time frame: Pre-dose up to 24 hours post-dose

  9. Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours After Dosing (AUC 0-8h) of Evobrutinib

    Time frame: Pre-dose up to 8 hours post-dose

  10. Apparent Clearance (CL/f) of Evobrutinib

    Time frame: Pre-dose up to 30 hours post-dose

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

    Time frame: Pre-dose up to 30 hours post-dose

  12. Amount of Unchanged Drug (Evobrutinib) Excreted in Urine During Collection Interval (0-8 hours) (Ae0-8h)

    Time frame: Pre-dose up to 8 hours post-dose

  13. Fraction of Administered Drug (Evobrutinib) Excreted in Urine (fe)

    Time frame: Pre-dose up to 30 hours post-dose

  14. Fraction of Unbound Drug (Evobrutinib) in the Plasma (fu)

    Time frame: Pre-dose up to 30 hours post-dose

  15. Renal Clearance of Evobrutinib (CLR)

    Time frame: Pre-dose up to 30 hours post-dose

  16. Non-Renal Clearance of Evobrutinib (CLNonR/f)

    Time frame: Pre-dose up to 30 hours post-dose

Sponsors and collaborators

Lead sponsor

Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

Phase I, Open-label, Single Dose Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics (PK) of Evobrutinib (M2951) Compared to Normal Renal Function in Male and Female Subjects

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Feb 19, 2018
Registry last updated
May 16, 2019

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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