A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012)

A 2-part, Open-label, Single-dose Study to Investigate the Influence of Hepatic Impairment on the Pharmacokinetics of MK-8189

The purpose of this study is to compare the pharmacokinetics (PK) of MK-8189 in participants with moderate hepatic impairment (based on the Child-Pugh classification) to healthy participants. This is Part 1 of the study; following review of the safety and PK data from Part 1, a decision will be made as to whether Part 2 of the study will be initiated. If done, Part 2 of the study will compare the PK of MK-8189 in participants with mild hepatic impairment to healthy participants.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: MK-8189

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento Inc. ( Site 0002)
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Is a continuous non-smoker or moderate smoker (of fewer than 20 cigarettes/day or equivalent)
• Female participant is not pregnant or breastfeeding and is not woman of childbearing potential (WOCBP) or is a WOCBP using contraception or abstinent from heterosexual intercourse during the intervention period and for at least 14 days after the last dose of study intervention
• (For hepatically impaired participants) Has a diagnosis of chronic (>6 months), stable (no acute episodes within the previous 2 months due to deterioration in hepatic function) hepatic impairment

Exclusion Criteria:

• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
• Has a history of cancer; exceptions include (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, (2) other successfully treated malignancies
• Has a history of significant multiple and/or severe allergies or has had significant intolerability to prescription or non-prescription drugs or food
• Is positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
• Has had major surgery or lost 1 unit of blood within 4 weeks prior to prestudy visit
• Consumes greater than 3 glasses of alcoholic beverages per day
• Consumes greater than 6 servings (1 serving is ~120 mg of caffeine) caffeinated beverages per day
• (For hepatically impaired participants) Is taking medications to treat chronic medical conditions and has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of the medications during study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Hepatic Impairment Participants; Participants with hepatic impairment will receive a single dose of MK-8189 4 mg orally on Day 1.	Drug: MK-8189; Administered at a dose of 4 mg via oral tablet
Experimental: Healthy Participants; Healthy participants will receive a single dose of MK-8189 4 mg orally on Day 1.	Drug: MK-8189; Administered at a dose of 4 mg via oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189	AUC0-inf is a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood samples collected pre and post-dose at multiple timepoints were used to estimate AUC0-inf following MK-8189 administration. Geometric least-squares mean and confidence intervals for AUC0-inf were calculated using a linear fixed effects model performed on natural log-transformed values.	Pre-dose (0), 2, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose (hepatic impairment and healthy participants); 60, 84, 108 and 120 hours post-dose (hepatic impairment participants)
Maximum Observed Plasma Concentration (Cmax) of MK-8189	Cmax is the maximum concentration of MK-8189 observed in plasma. Blood samples collected pre and post-dose at multiple timepoints were used to estimate Cmax following MK-8189 administration. Geometric least-squares mean and confidence intervals of Cmax were calculated using a linear fixed effects model performed on natural log-transformed values.	Pre-dose (0), 2, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose (hepatic impairment and healthy); 60, 84, 108 and 120 hours post-dose (hepatic impairment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be reported.	Up to approximately 15 days
Number of Participants Who Discontinue From the Study Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study due to an AE will be reported.	Up to approximately 15 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): January 16, 2022
• Study Completion (Actual): January 25, 2022

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 8189-012; MK-8189-012 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No