Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates

NCT ID: NCT05064488

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-04
• Study Completion Date: 2021-12-10

Brief Summary

This study consisted of 2 parts: Part 1 and 2. The purpose of this study was to evaluate the pharmacokinetic, safety and tolerability of multiple doses of evobrutinib on single doses of digoxin, metformin and rosuvastatin in Part-1 and sumatriptan in Part-2 of the study.

Conditions

Healthy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Cocktail (Day 1)

Participants received single oral dose of Cocktail (digoxin 0.25 mg tablet, metformin 10 mg solution, rosuvastatin 10 mg tablet) on Day 1 in Part 1 under fed conditions.

Group Type: EXPERIMENTAL

Digoxin (0.25mg)

Intervention Type: DRUG

Participants received single oral dose of digoxin tablet (0.25 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Metformin (10mg)

Intervention Type: DRUG

Participants received single oral dose of metformin 10 mg solution on Day 1 and Day 10 in Part 1 under fed conditions.

Rosuvastatin (10mg)

Intervention Type: DRUG

Participants received single oral dose of rosuvastatin tablet (10 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Part 1: Evobrutinib (Days 4 to 12)

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day on Days 4 to 12 in Part 1 under fed conditions.

Group Type: EXPERIMENTAL

Evobrutinib (45mg)

Intervention Type: DRUG

Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions.

Part 1: Evobrutinib + Cocktail (Day 10)

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and cocktail (digoxin 0.25 mg tablet, metformin 10 mg solution, rosuvastatin 10 mg tablet) on Day 10 in Part 1 under fed conditions.

Group Type: EXPERIMENTAL

Evobrutinib (45mg)

Intervention Type: DRUG

Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions.

Digoxin (0.25mg)

Intervention Type: DRUG

Participants received single oral dose of digoxin tablet (0.25 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Metformin (10mg)

Intervention Type: DRUG

Participants received single oral dose of metformin 10 mg solution on Day 1 and Day 10 in Part 1 under fed conditions.

Rosuvastatin (10mg)

Intervention Type: DRUG

Participants received single oral dose of rosuvastatin tablet (10 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Part 2: Sumatriptan (Day 1)

Participants received single oral dose of Sumatriptan 25 mg tablet on Day 1 in Part 2 under fed conditions.

Group Type: EXPERIMENTAL

Sumatriptan (25mg)

Intervention Type: DRUG

Participants received single dose of sumatriptan tablet (25 mg) on Day 1 and Day 8 in Part 2 under fed conditions.

Part 2: Evobrutinib (Days 2 to 8)

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day on Days 2 to 8 in Part 2 under fed conditions.

Group Type: EXPERIMENTAL

Evobrutinib (45mg)

Intervention Type: DRUG

Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions.

Part 2: Evobrutinib + Sumatriptan (Day 8)

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and single oral dose of Sumatriptan 25 mg tablet on Day 8 in Part 2 under fed conditions.

Group Type: EXPERIMENTAL

Evobrutinib (45mg)

Intervention Type: DRUG

Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions.

Sumatriptan (25mg)

Intervention Type: DRUG

Participants received single dose of sumatriptan tablet (25 mg) on Day 1 and Day 8 in Part 2 under fed conditions.

Interventions

Evobrutinib (45mg)

Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions.

Intervention Type: DRUG

Digoxin (0.25mg)

Participants received single oral dose of digoxin tablet (0.25 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Intervention Type: DRUG

Metformin (10mg)

Participants received single oral dose of metformin 10 mg solution on Day 1 and Day 10 in Part 1 under fed conditions.

Intervention Type: DRUG

Rosuvastatin (10mg)

Participants received single oral dose of rosuvastatin tablet (10 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Intervention Type: DRUG

Sumatriptan (25mg)

Participants received single dose of sumatriptan tablet (25 mg) on Day 1 and Day 8 in Part 2 under fed conditions.

Intervention Type: DRUG

Other Intervention Names

M2951

Eligibility Criteria

Inclusion Criteria

• Participants were 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 had a body weight within 50.0 and 100.0 kilograms [kg] (inclusive) and body mass index within the range of 19.0 and 30.0 kilograms per square meter [kg/m^2] (inclusive)

Exclusion Criteria

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
• Individuals with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease were excluded from the study
• Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening
• History of any malignancy
• 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 Screening
• History of shingles within 12 months prior to Screening
• 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, which may affect the safety of the participant and/or outcome of the study per the Investigator's discretion
• History of alcoholism or drug abuse within 2 years prior to Screening, or positive for drugs of abuse, nicotine/cotinine or alcohol by the laboratory assays conducted during Screening and Day -1
• History of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to or at the time of Screening
• Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening
• Moderate or strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A4/5) within 4 weeks prior to the 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-details/?id=MS200527_0078

Trial Awareness and Transparency website

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

Medical Information Location Map - Med Info Contacts

Other Identifiers

2021-001923-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200527_0078

Identifier Type: -

Identifier Source: org_study_id