Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK

NCT ID: NCT04546789

Last Updated: 2025-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2021-05-16

Brief Summary

This study was to investigate the pharmacokinetic (PK) and safety of M2951 (Bruton's tyrosine kinase [BTK] inhibitor) in participants with different degrees of hepatic impairment compared to participants with normal hepatic function.

Conditions

Hepatic Impairment

Study Design

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

Study Groups

Group 1: Normal Hepatic Function (Reference)

Participants with normal hepatic function received single oral dose of 30 milligrams (mg) M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast.

Group Type: EXPERIMENTAL

M2951 (BTK inhibitor)

Intervention Type: DRUG

Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.

Group 2: Mild Hepatic Impairment

Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 30 mg M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. The Child-Pugh Score was a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon serum albumin, ascites, serum bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.

Group Type: EXPERIMENTAL

M2951 (BTK inhibitor)

Intervention Type: DRUG

Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.

Group 3: Moderate Hepatic Impairment

Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 30 mg M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. The Child-Pugh Score was a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon serum albumin, ascites, serum bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.

Group Type: EXPERIMENTAL

M2951 (BTK inhibitor)

Intervention Type: DRUG

Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.

Interventions

M2951 (BTK inhibitor)

Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.

Intervention Type: DRUG

Other Intervention Names

Evobrutinib

Eligibility Criteria

Inclusion Criteria

• Participants with normal hepatic function only will be 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 OR
• Participants with moderately impaired hepatic function only will be considered to have moderately (Child-Pugh class B and confirmed liver cirrhosis) impaired hepatic function and has been clinically stable for at least 1 month prior to Screening OR
• Participants with mildly impaired hepatic function only will be considered to have mildly (Child-Pugh class A and confirmed liver cirrhosis) impaired hepatic function and has been clinically stable for at least 1 month prior to Screening
• Have a body weight within 50.0 and 120.0 kilogram (kg) and body mass index (BMI) within the range 19.0 and 36.0 kilogram per square meter (kg/m^2)
• Female participants are not pregnant or breastfeeding, and at least one of the following conditions applies
• Not a woman of childbearing potential (WOCBP)

Exclusion Criteria

• Clinical history of autoimmune disorder with hepatic influence (Hashimoto thyroiditis and rheumatic diseases allowed)
• History of any malignancy
• Diseases and surgeries of the gastrointestinal tract, which could influence the gastrointestinal anatomy and mobility. Prior history of cholecystectomy or inflammatory bowel disease, and any clinically relevant surgery within 6 months prior to Screening
• 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 trial per the Investigator's discretion
• Participants with impaired hepatic function will be excluded who had Primary and secondary biliary cirrhosis.
• Participants with impaired hepatic function will be excluded with Clinical evidence of severe ascites.
• Participants with impaired hepatic function will be excluded with Hepatic encephalopathy Grade greater than 1

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 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

CRS Clinical Research Services Kiel GmbH

Kiel, , 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_0059

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

2020-001920-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200527_0059

Identifier Type: -

Identifier Source: org_study_id