Hepatic Insufficiency
Conditions
Brief summary
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.
Interventions
DRUGBomedemstat
Capsule for oral administration
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of Bomedemstat in Participants with Mild Hepatic Impairment (HI) | Up to 216 hours | Blood samples collected to determine the AUC0-inf of bomedemstat. |
| Maximum Plasma Concentration (Cmax) of Bomedemstat in Participants with Mild HI | Up to 216 hours | Blood samples collected to determine the Cmax of bomedemstat. |
| AUC0-Inf of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples collected to determine the AUC0-inf of bomedemstat. |
| Cmax of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples collected to determine the Cmax of bomedemstat. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience an Adverse Event (AE) | Up to 14 days | 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. |
| Number of Participants Who Discontinue Study Due to an AE | Up to 14 days | 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 discontinuing study treatment due to an AE will be reported. |
| Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of Bomedemstat in Participants with Mild HI | Up to 216 hours | Blood samples will be collected to determine the AUC0-last of bomedemstat. |
| Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24hrs) of Bomedemstat in Participants with Mild HI | At designated timepoints up to 24 hours postdose | Blood samples will be collected to determine the AUC0-24hr of bomedemstat. |
| Plasma Concentration at 24 Hours (C24) of Bomedemstat in Participants with Mild HI | At designated timepoints up to 24 hours postdose | Blood samples will be collected to determine the C24 of bomedemstat. |
| Time to Maximum Plasma Concentration (Tmax) of Bomedemstat in Participants with Mild HI | Up to 216 hours | Blood samples will be collected to determine the Tmax of bomedemstat. |
| Apparent Terminal Half-life (t1/2) of Bomedemstat in Participants with Mild HI | Up to 216 hours | Blood samples will be collected to determine the t1/2 of bomedemstat. |
| Apparent Clearance (CL/F) of Bomedemstat in Participants with Mild HI | Up to 216 hours | Blood samples will be collected to determine the CL/F of bomedemstat. |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of Bomedemstat in Participants with Mild HI | Up to 216 hours | Blood samples will be collected to determine the Vz/F of bomedemstat. |
| AUC0-Last of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples will be collected to determine the AUC0-last of bomedemstat. |
| AUC0-24hrs of Bomedemstat in Participants with Moderate HI | At designated timepoints up to 24 hours postdose | Blood samples will be collected to determine the AUC0-24hr of bomedemstat. |
| C24 of Bomedemstat in Participants with Moderate HI | At designated timepoints up to 24 hours postdose | Blood samples will be collected to determine the C24 of bomedemstat. |
| Tmax of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples will be collected to determine the Tmax of bomedemstat. |
| t1/2 of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples will be collected to determine the t1/2 of bomedemstat. |
| CL/F of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples will be collected to determine the CL/F of bomedemstat. |
| Vz/F of Bomedemstat in Participants with Moderate HI | Up to 216 hours | Blood samples will be collected to determine the Vz/F of bomedemstat. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed