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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04676425
• Other study ID #: 8189-012
• Secondary ID: MK-8189-012
• Status: Completed
• Phase: Phase 1
• Start date: March 17, 2021
• Est. completion date: January 25, 2022

Study information

• Verified date: December 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: January 25, 2022
• Est. primary completion date: January 16, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• MK-8189
Administered at a dose of 4 mg via oral tablet

Locations

Country	Name	City	State
United States	ProSciento Inc. ( Site 0002)	Chula Vista	California
United States	Clinical Pharmacology of Miami ( Site 0001)	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	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