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

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Healthy Participants	MK-8189	Healthy participants will receive a single dose of MK-8189 4 mg orally on Day 1.
Moderate Hepatic Impairment Participants	MK-8189	Participants with hepatic impairment will receive a single dose of MK-8189 4 mg orally on Day 1.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of MK-8189	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)	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.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189	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)	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Experience One or More Adverse Events (AEs)	Up to approximately 15 days	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.
Number of Participants Who Discontinue From the Study Due to an AE	Up to approximately 15 days	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.

Locations (2): Clinical Pharmacology of Miami ( Site 0001)
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Miami, Florida, United States
ProSciento Inc. ( Site 0002)
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Chula Vista, California, United States