Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany24 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatic Impairment

Interventions

M2951 (BTK inhibitor)DRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 79 YearsHealthy volunteers:

Medical Language ↔ Plain English

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) * Other protocol defined inclusion criteria could apply 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 * Other protocol defined exclusion criteria could apply

Locations (1)

CRS Clinical Research Services Kiel GmbH

Kiel, Germany

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

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

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events that started or worsened that in severity after at least one dose of the study intervention has been administered. TEAEs included both serious TEAEs and non-serious TEAEs.

Time frame: up to follow-up (Day 6)

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

Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets and reticulocytes. Change from baseline in hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, and reticulocytes at Day 2 and Day 6 were reported.

Data from ClinicalTrials.gov

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