Relative Bioavailability of Evobrutinib Tablet Batches

NCT07214922 | Completed Phase 1 Results

• 2 other identifiers: MS200527_01312022-002755-19
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

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

  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.

  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

• Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

  Cmax was obtained directly from the concentration versus time curve.

  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

Secondary Outcomes (15)

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

  Up to 34 days

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

  Up to 34 days

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

  Baseline (Pre-dose), 2 hours post-dose

• Change From Baseline in Vital Signs: Temperature

  Baseline (Pre-dose), 2 hours post-dose

• Change From Baseline in Vital Signs: Pulse Rate

  Baseline (Pre-dose), 2 hours post-dose

Study Arms (4)

Evobrutinib: Treatment Sequence 1: ABCD

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D

Evobrutinib: Treatment Sequence 2: BDAC

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D

Evobrutinib: Treatment Sequence 3: CADB

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D

Evobrutinib: Treatment Sequence 4: DCBA

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D

Interventions

Treatment A DRUG

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

Also known as: Evobrutinib

Evobrutinib: Treatment Sequence 1: ABCD; Evobrutinib: Treatment Sequence 2: BDAC; Evobrutinib: Treatment Sequence 3: CADB; Evobrutinib: Treatment Sequence 4: DCBA

Treatment B DRUG

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

Also known as: Evobrutinib

Evobrutinib: Treatment Sequence 1: ABCD; Evobrutinib: Treatment Sequence 2: BDAC; Evobrutinib: Treatment Sequence 3: CADB; Evobrutinib: Treatment Sequence 4: DCBA

Treatment C DRUG

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

Also known as: Evobrutinib

Evobrutinib: Treatment Sequence 1: ABCD; Evobrutinib: Treatment Sequence 2: BDAC; Evobrutinib: Treatment Sequence 3: CADB; Evobrutinib: Treatment Sequence 4: DCBA

Treatment D DRUG

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

Also known as: Evobrutinib

Evobrutinib: Treatment Sequence 1: ABCD; Evobrutinib: Treatment Sequence 2: BDAC; Evobrutinib: Treatment Sequence 3: CADB; Evobrutinib: Treatment Sequence 4: DCBA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Interventions

evobrutinib

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2025
• First Posted: October 9, 2025
• Study Start: January 18, 2023
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)