DDI Study of Evobrutinib and Carbamazepine

NCT05248945 | Completed Phase 1 Results

• 2 other identifiers: MS200527_01082021-003381-13
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details included: Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants were residents in the Clinical Research Unit from Day 1 to Day 20 and returned on Day 26 for a Safety Follow-Up visit.

Conditions

Healthy

Keywords

Clinical Pharmacology

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-Time Curve (AUC) 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 (LLQ) 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.

  Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.

• Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

  Cmax was obtained from plasma concentration time curve.

  Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 16 and 24 hours post dose on Day 1 and Day 19.

Secondary Outcomes (33)

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

  Baseline (Day 1) and Day 26

• Absolute Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes Values

  Baseline (Day 1) and Day 26

• Absolute Change From Baseline in Hematology Parameter: Hemoglobin Levels

  Baseline (Day 1) and Day 26

• Absolute Change From Baseline in Hematology Parameter: Hematocrit Values

  Baseline (Day 1) and Day 26

• Absolute Change From Baseline in Hematology Parameter: Activated Partial Thromboplastin Time

  Baseline (Day 1) and Day 26

Study Arms (1)

Evobrutinib plus Carbamazepine

EXPERIMENTAL

Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19 under fed condition followed by Cabamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily.

Drug: Evobrutinib; Drug: Carbamazepine

Interventions

Evobrutinib DRUG

Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19

Also known as: M2951

Evobrutinib plus Carbamazepine

Carbamazepine DRUG

Participants received Carbamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily.

Evobrutinib plus Carbamazepine

Eligibility Criteria

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

You may qualify if:

• Type of Participant and Disease Characteristics
• Had a body weight within 50.0 and 100.0 kg (kilogram) (inclusive) and Body Mass Index (BMI) within the range 19.0 and 30.0 kilogram per meter square (kg/m\^2) (inclusive)
• Male: No contraception and barrier requirements were needed. Female: Was not a woman of childbearing potential
• Were capable of giving signed informed consent, which included compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol
• Were stable nonsmokers for at least 3 months preceding Screening

You may not qualify if:

• Had a 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
• Had been administered live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g., SARSCoV2 vaccines) was allowed until 2 weeks before admission to Clinical Research Unit (CRU), thereafter it was prohibited until the end of the study
• Had been administered moderate or strong inhibitors or inducers of Cytochrome P450 (CYP)3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention
• Had a contraindication to carbamazepine (carbamazepine SmPC)
• Had a history of any malignancy
• Had a history of drug hypersensitivity ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other hypersensitivity reaction in general, including contact hypersensitivity to Electrocardiogram (ECG) electrodes, which may have affected the safety of the participant and/or outcome of the study per the Investigator's discretion.

Sponsors & Collaborators

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

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, Bavaria, Germany

Location

Related Links

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

MeSH Terms

Interventions

evobrutinib; Carbamazepine

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: February 21, 2022
• Study Start: January 13, 2022
• Primary Completion: July 18, 2022
• Study Completion: July 18, 2022
• Last Updated: January 15, 2026
• Results First Posted: January 15, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)