Relative Bioavailability of Evobrutinib Tablet Batches

NCT ID: NCT07214922

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-18
• Study Completion Date: 2023-02-24

Brief Summary

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.

Conditions

Healthy

Keywords

Evobrutinib; Pharmacokinetics; Relative Bioavailability; Crossover

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Evobrutinib: Treatment Sequence 1: ABCD

Participants will receive single oral dose of Treatment A on Day 1 in period 1, followed by single oral dose of Treatment B on Day 3 in period 2, followed by Treatment C on Day 5 in period 3 and followed by single oral dose of Treatment D on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

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

Treatment B

Intervention Type: DRUG

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

Treatment C

Intervention Type: DRUG

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

Treatment D

Intervention Type: DRUG

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

Evobrutinib: Treatment Sequence 2: BDAC

Participants will receive single oral dose of Treatment B on Day 1 in period 1, followed by single oral dose of Treatment D on Day 3 in period 2, followed by Treatment A on Day 5 in period 3 and followed by single oral dose of Treatment C on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

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

Treatment B

Intervention Type: DRUG

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

Treatment C

Intervention Type: DRUG

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

Treatment D

Intervention Type: DRUG

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

Evobrutinib: Treatment Sequence 3: CADB

Participants will receive single oral dose of Treatment C on Day 1 in period 1, followed by single oral dose of Treatment A on Day 3 in period 2, followed by Treatment D on Day 5 in period 3 and followed by single oral dose of Treatment B on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

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

Treatment B

Intervention Type: DRUG

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

Treatment C

Intervention Type: DRUG

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

Treatment D

Intervention Type: DRUG

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

Evobrutinib: Treatment Sequence 4: DCBA

Participants will receive single oral dose of Treatment D on Day 1 in period 1, followed by single oral dose of Treatment C on Day 3 in period 2, followed by Treatment B on Day 5 in period 3 and followed by single oral dose of Treatment A on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

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

Treatment B

Intervention Type: DRUG

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

Treatment C

Intervention Type: DRUG

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

Treatment D

Intervention Type: DRUG

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

Interventions

Treatment A

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

Intervention Type: DRUG

Treatment B

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

Intervention Type: DRUG

Treatment C

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

Intervention Type: DRUG

Treatment D

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

Intervention Type: DRUG

Other Intervention Names

Evobrutinib; Evobrutinib; Evobrutinib; Evobrutinib

Eligibility Criteria

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

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

1. hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or Human Immunodeficiency Virus (HIV) I and II tests at Screening

2. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

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

Locations

Nuvisan GmbH

Neu-Ulm, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/

Trial Awareness and Transparency website

http://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html

Medical Information Location Map - Med Info Contacts

Other Identifiers

2022-002755-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200527_0131

Identifier Type: -

Identifier Source: org_study_id