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Completed

NCT Number: NCT07214922

Relative Bioavailability of Evobrutinib Tablet Batches

The main purpose of the study is to compare the Pharmacokinetics (PK), safety and tolerability of different manufacturing batches of M2951 tablet formulation relative to a reference batch under fasted conditions in healthy participants.

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Participants who are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection, or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
  • Participants who have a body weight within 50.0 and 100.0 kilogram (kg) (inclusive) and Body Mass Index within the range 19.0 and 30.0 kg/ meter square (m2) (inclusive)
  • Female participant who agrees to use appropriate contraception and barrier methods.
  • Male participants: No contraception needed
  • Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and this protocol
  • Participants who are stable non-smokers for at least 3 months preceding Screening
  • Other protocol defined inclusion criteria could apply

Exclusion criteria

  • Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, musculoskeletal, genitourinary, immunological, dermatological, connective tissue, psychiatric (due to rare risk of hallucinations, agitation and activation of psychosis), and other diseases or disorders, and epilepsy, as determined by medical evaluation
  • Participants with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study
  • Participants with prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to the first administration of study intervention
  • Participants with history of any malignancy
  • Participants with history of seizures
  • Participants with history of pharmacologically treated psychiatric disease
  • Participants with history of chronic or recurrent acute infection or any bacterial, viral, parasitic or fungal infections within 30 days prior to Screening and at any time between Screening and admission, or hospitalization due to infection within 6 months prior to the first administration of study intervention
  • Participants with history of shingles within 12 months prior to Screening
  • Participants with history of drug hypersensitivity
  • Participants with history of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to or at the time of Screening
  • Participants positive for
  • hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or Human Immunodeficiency Virus (HIV) I and II tests at Screening
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening and Day -1
  • Participants with any condition, including findings in the laboratory tests, medical history (example heart failure, hypokalemia, family history of Long QT Syndrome), 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
  • Participants with history of administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Day 1.
  • Participants with history of administration of other types of vaccines is allowed until 14 days before the first administration of study intervention, thereafter it is prohibited until the end of the study.
  • Participants with Moderate or strong inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4)/5 or Pgp within 4 weeks prior to the first administration of study intervention
  • Participants with use of any prescribed medicine or over-the-counter drug or dietary supplement, including herbal remedies, vitamins, and minerals, antacids and dietary supplements such as fish oils within 2 weeks or 5 times the half-life of the respective drug, whichever is longer, prior to the first administration of study intervention
  • Participants with use of any investigational drug in any clinical study within 60 days prior to Day 1 administration, or have used an experimental monoclonal antibody within the past 1 year prior to Day 1, or have participated in a study evaluating a Bruton Tyrosine Kinase (BTK) inhibitor within 60 days, or are on extended follow-up in a clinical study, even if last administration of a study intervention was more than 60 days ago, or 5 half-lives of the investigational drug, whichever is longer, prior to the first administration of study intervention
  • Participants with a medical history and physical examination results that include any ongoing clinically relevant findings as judged by the Investigator
  • Participants with clinically relevant findings (excluding minor, not clinically relevant excursions from normal ranges, as judged by the Investigator) at Screening in biochemistry, hematology, coagulation, and urinalysis examinations for the age of the participant, as judged by the Investigator:
  • Alanine aminotransferase, aspartate aminotransferase: above upper limit of normal (ULN)
  • Creatinine: above normal limits
  • Absolute lymphocyte count, absolute neutrophil count: below limit of reference range.
  • Amylase and lipase above normal ranges; minor deviations are allowed, if not clinically relevant.
  • Participants with estimated glomerular rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation (2009) < 90 milliliters/minute(mL/min) at Screening. In case of a borderline result between ≥ 80 and < 90 mL/min, Cystatin C will be determined in addition, and the participant will only be included if the Cystatin C value is below the upper limit of normal
  • Participants with semi-supine systolic blood pressure > 140 mmHg or < 90 millimeters of mercury (mmHg), diastolic blood pressure > 90 mmHg or < 50 mmHg, and pulse rate > 90 or < 50 beats per minute (bpm) at Screening.
  • Participants with consumption of alcohol from 48 hours prior to first administration of study intervention.
  • Other protocol defined exclusion criteria could apply

Treatment and study plan

Treatment A

Drug

Participants will receive single dose of Treatment A in treatment period 1, 2, 3 or 4 under fasted conditions.

Other names: Evobrutinib

Treatment B

Drug

Participants will receive single dose of Treatment B in treatment period 1, 2, 3 or 4 under fasted conditions.

Other names: Evobrutinib

Treatment C

Drug

Participants will receive single dose of Treatment C in treatment period 1, 2, 3 or 4 under fasted conditions.

Other names: Evobrutinib

Treatment D

Drug

Participants will receive single dose of Treatment D in treatment period 1, 2, 3 or 4 under fasted conditions.

Other names: Evobrutinib

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  2. Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    Cmax was obtained directly from the concentration versus time curve.

Secondary outcomes

  1. Number of Participants With Treatment- Emergent Adverse Events (TEAEs)

    Time frame: Up to 34 days

    An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs.

  2. Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity

    Time frame: Up to 34 days

    The Investigator assessed the severity of each AE and SAE reported during the study and assign it to one of the following categories: Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities; Severe: An event that prevents normal everyday activities. Do not confuse an AE that is assessed as severe with a SAE. Severe is a category used to rate the intensity of an event; both AEs and SAEs can be assessed as severe.

  3. Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure

    Time frame: Baseline (Pre-dose), 2 hours post-dose

    Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.

  4. Change From Baseline in Vital Signs: Temperature

    Time frame: Baseline (Pre-dose), 2 hours post-dose

    Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.

  5. Change From Baseline in Vital Signs: Pulse Rate

    Time frame: Baseline (Pre-dose), 2 hours post-dose

    Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.

  6. Change From Baseline in Vital Signs: Respiratory Rate

    Time frame: Baseline (Pre-dose), 2 hours post-dose

    Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.

  7. Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate

    Time frame: Baseline (Pre-dose), 2 hours post-dose

    Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions

  8. Change From Baseline in Electrocardiograms (ECGs) Parameter: RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration

    Time frame: Baseline (Pre-dose), 2 hours post-dose

    RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.

  9. Number of Participants With Clinically Significant Changes in Laboratory Parameters

    Time frame: Screening up to Day 8

    Laboratory investigation included hematology, biochemistry and urinalysis. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.

  10. Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).

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

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

  12. Terminal Half Life (T1/2) of Evobrutinib

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.

  13. Apparent Total Body Clearance (CL/f) of Evobrutinib

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for Evobrutinib.

  14. Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    Vz/f is defined as the apparent volume of distribution during the terminal phase following extravascular administration for Evobrutinib.

  15. Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero Extrapolated to Infinity [Frel(AUC0-inf)] of Evobrutinib (Treatment B, C and D) Compared to Evobrutinib Reference Treatment A

    Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

    Relative Bioavailability in percentage of each treatment (B, C, and D) in relation to the reference Treatment (A) was calculated as Frel = 100 multiplied by (AUC0-inf [treatment B, C, D]) multiplied by Dose [treatment A] divided by (AUC0-inf [treatment A]) multiplied by Dose [treatment B, C, D]. Treatment A to determine relative bioavailability.

Sponsors and collaborators

Lead sponsor

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

A Phase I, Open-Label Study of the Relative Bioavailability of Evobrutinib Tablet Manufacturing Batches in Healthy Participants

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Oct 9, 2025
Registry last updated
Dec 23, 2025

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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