NCT04676425

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

Completed Phase 1 Results posted Last updated 6 October 2023

What this trial tests

Phase 1 trial testing MK-8189 in Hepatic Impairment in 14 participants. Completed in 25 January 2022.

Timeline

17 March 2021

Primary endpoint
16 January 2022

25 January 2022

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	14
Start date	17 March 2021
Primary completion	16 January 2022
Estimated completion	25 January 2022
Sites	2 locations across United States

Drugs / interventions tested

• MK-8189 — full drug profile →

Conditions studied

• Hepatic Impairment — all drugs for Hepatic Impairment →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189 Primary · 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.

Group	Value	95% CI
Moderate Hepatic Impairment Participants	5600	3020 – 10400
Healthy Participants	4710	3340 – 6660

Maximum Observed Plasma Concentration (Cmax) of MK-8189 Primary · 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.

Group	Value	95% CI
Moderate Hepatic Impairment Participants	194	127 – 296
Healthy Participants	158	131 – 191

Number of Participants Who Experience One or More Adverse Events (AEs) Secondary · 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.

Group	Value	95% CI
Moderate Hepatic Impairment Participants	4
Healthy Participants	0

Number of Participants Who Discontinue From the Study Due to an AE Secondary · 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.

Group	Value	95% CI
Moderate Hepatic Impairment Participants	0
Healthy Participants	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 15 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Moderate Hepatic Impairment Participants

Serious: 0/7 (0%)

Deaths: 0/7

Healthy Participants

Serious: 0/7 (0%)

Deaths: 0/7

Other adverse events (10 terms — click to expand)

Reaction	System	Moderate Hepatic Impairmen…	Healthy Participants
Vomiting	Gastrointestinal disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Affect lability	Psychiatric disorders	—	—
Anxiety	Psychiatric disorders	—	—
Hot flush	Vascular disorders	—	—
Hypotension	Vascular disorders	—	—

Data from ClinicalTrials.gov NCT04676425 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.