A Study of Bomedemstat (MK-3543) in Participants With Mild or Moderate Hepatic Impairment (MK-3543-023)

Merck Sharp & Dohme LLC9 enrolled

Overview

The purpose of this study is to learn what happens to bomedemstat (MK-3543) in a person's body over time. Researchers will compare what happens to bomedemstat in the body when it is given to participants with mild or moderate hepatic (liver) impairment and healthy participants. Participants will be allocated to one of three groups: mild hepatic impairment (HI), moderate HI, or healthy matched control. All participants will receive a single oral dose of bomedemstat on Day 1. Healthy control participants will be enrolled after hepatic impairment participants have been dosed. Healthy control participants will be matched for the mean age and mean body-mass index (BMI) of all participants with HI (mild and moderate HI combined) and sex to each HI group separately.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatic Insufficiency

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria The main inclusion criteria include but are not limited to the following: * Is a non-smoker or is a moderate smoker for at least 3 months prior to dosing Participants with Mild and Moderate HI * Is classified as having either mild HI (Group 1) or moderate HI (Group 2) score on the Child-Pugh scale ranging from 5 to 6 (mild) or 7 to 9 (moderate) * Has a diagnosis of chronic (\> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology Healthy Control Participants: * Must match the mean age (± 15 years) of participants with mild HI and moderate HI * Must match the mean body-mass index (BMI) (± 25%) of participants with mild HI (Group 1) and moderate HI * Must match the sex ratio (±2) of participants in each HI group, separately Exclusion Criteria The main exclusion criteria include but are not limited to the following: All Participants * History of cancer (malignancy) * Female participants of childbearing potential * Is positive for Hepatitis C virus (HCV) * Is positive for Hepatitis B surface antigen (HBsAg) * Is positive for human immunodeficiency virus (HIV) Participants with Mild and Moderate HI * Has any significant arrhythmia or conduction abnormality * Severe complications of liver disease within the preceding 3 months * Primary biliary cholangitis or biliary obstruction * Has a history of a recent variceal bleeds * Has evidence of hepatorenal syndrome * Has a history of liver or other solid organ transplantation * Has an active infection requiring systemic therapy * Requires paracentesis more often than 2 times per month * Has transjugular intrahepatic portosystemic shunt and/or has undergone portacaval shunting Healthy Control Participants * Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases * Is a regular user of cannabis products within approximately 6 months of study

Locations (3)

University of Miami ( Site 0003)

Miami, Florida, United States

Orlando Clinical Research Center ( Site 0001)

Orlando, Florida, United States

The Texas Liver Institute ( Site 0002)

San Antonio, Texas, United States

Outcomes

Primary Outcomes

Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of Bomedemstat in Participants with Mild Hepatic Impairment (HI)

Blood samples collected to determine the AUC0-inf of bomedemstat.

Time frame: Up to 216 hours

Maximum Plasma Concentration (Cmax) of Bomedemstat in Participants with Mild HI

Blood samples collected to determine the Cmax of bomedemstat.

Time frame: Up to 216 hours

AUC0-Inf of Bomedemstat in Participants with Moderate HI

Blood samples collected to determine the AUC0-inf of bomedemstat.

Time frame: Up to 216 hours

Cmax of Bomedemstat in Participants with Moderate HI

Blood samples collected to determine the Cmax of bomedemstat.

Time frame: Up to 216 hours

Secondary Outcomes

Number of Participants Who Experience an Adverse Event (AE)

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported.

Time frame: Up to 14 days

Number of Participants Who Discontinue Study Due to an AE

Time frame: Up to 14 days

Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the AUC0-last of bomedemstat.

Time frame: Up to 216 hours

Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24hrs) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the AUC0-24hr of bomedemstat.

Time frame: At designated timepoints up to 24 hours postdose

Plasma Concentration at 24 Hours (C24) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the C24 of bomedemstat.

Time frame: At designated timepoints up to 24 hours postdose

Time to Maximum Plasma Concentration (Tmax) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the Tmax of bomedemstat.

Time frame: Up to 216 hours

Apparent Terminal Half-life (t1/2) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the t1/2 of bomedemstat.

Time frame: Up to 216 hours

Apparent Clearance (CL/F) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the CL/F of bomedemstat.

Time frame: Up to 216 hours

Apparent Volume of Distribution During Terminal Phase (Vz/F) of Bomedemstat in Participants with Mild HI

Blood samples will be collected to determine the Vz/F of bomedemstat.

Time frame: Up to 216 hours

AUC0-Last of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the AUC0-last of bomedemstat.

Time frame: Up to 216 hours

AUC0-24hrs of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the AUC0-24hr of bomedemstat.

Time frame: At designated timepoints up to 24 hours postdose

C24 of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the C24 of bomedemstat.

Time frame: At designated timepoints up to 24 hours postdose

Tmax of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the Tmax of bomedemstat.

Time frame: Up to 216 hours

t1/2 of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the t1/2 of bomedemstat.

Time frame: Up to 216 hours

CL/F of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the CL/F of bomedemstat.

Time frame: Up to 216 hours

Vz/F of Bomedemstat in Participants with Moderate HI

Blood samples will be collected to determine the Vz/F of bomedemstat.

Time frame: Up to 216 hours