Clinical trial NCT04676425: A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012)
Official title: A 2-part, Open-label, Single-dose Study to Investigate the Influence of Hepatic Impairment on the Pharmacokinetics of MK-8189
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) of MK-8189
timeFrame: 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 outcomes:
measure: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 15 days
measure: Number of Participants Who Discontinue From the Study Due to an AE
timeFrame: Up to approximately 15 days
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: ProSciento Inc. ( Site 0002)
state: California
city: Miami
country: United States
facility: Clinical Pharmacology of Miami ( Site 0001)
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: