A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Hepatic Impairment 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 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
|
Outcome Measures
Primary Outcome Measures
- Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of MK-8189 [1 hour 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)]
AUC0-inf is a measure of the total amount of drug in the plasma from the dose administration to the last measurable sample. Blood samples collected pre and post-dose at multiple timepoints will be used to estimate AUC0-inf following MK-8189 administration.
- Maximum observed plasma concentration (Cmax) of MK-8189 [1 hour 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 will be used to estimate Cmax following MK-8189 administration.
Secondary Outcome Measures
- Number of participants who experience one or more adverse events (AEs) [Up to ~Day 15]
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 ~Day 15]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Is a continuous non-smoker or moderate smoker (of fewer than 20 cigarettes/day or equivalent)
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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
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(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:
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Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
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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
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Has a history of significant multiple and/or severe allergies or has had significant intolerability to prescription or non-prescription drugs or food
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Is positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
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Has had major surgery or lost 1 unit of blood within 4 weeks prior to prestudy visit
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Consumes greater than 3 glasses of alcoholic beverages per day
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Consumes greater than 6 servings (1 serving is ~120 mg of caffeine) caffeinated beverages per day
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(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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ProSciento Inc. ( Site 0002) | Chula Vista | California | United States | 91911 |
| 2 | Clinical Pharmacology of Miami ( Site 0001) | Miami | Florida | United States | 33014 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8189-012
- MK-8189-012