Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK

NCT04546789 | Completed Phase 1 Results

• 2 other identifiers: MS200527_00592020-001920-32
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Keywords

Hepatic Impairment; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951

  AUC0-inf was calculated by combining AUC0-tlast 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, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of M2951

  Cmax was obtained directly from the plasma concentration versus time curve.

  Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose

Secondary Outcomes (32)

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

  up to follow-up (Day 6)

• Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes

  Baseline, Day 2 and follow-up (Day 6)

• Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes

  Baseline, Day 2 and follow-up (Day 6)

• Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

  Baseline, Day 2 and follow-up (Day 6)

• Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume

  Baseline, Day 2 and follow-up (Day 6)

Study Arms (3)

Group 1: Normal Hepatic Function (Reference)

EXPERIMENTAL

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.

Drug: M2951 (BTK inhibitor)

Group 2: Mild Hepatic Impairment

EXPERIMENTAL

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.

Drug: M2951 (BTK inhibitor)

Group 3: Moderate Hepatic Impairment

EXPERIMENTAL

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.

Drug: M2951 (BTK inhibitor)

Interventions

M2951 (BTK inhibitor) DRUG

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

Also known as: Evobrutinib

Group 1: Normal Hepatic Function (Reference); Group 2: Mild Hepatic Impairment; Group 3: Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

CRS Clinical Research Services Kiel GmbH

Kiel, 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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 14, 2020
• Study Start: September 30, 2020
• Primary Completion: May 16, 2021
• Study Completion: May 16, 2021
• Last Updated: October 28, 2025
• Results First Posted: October 28, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)