Trial Outcomes & Findings for A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012) (NCT NCT04676425)

Last Updated: 2023-10-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome 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)

Results posted on

2023-10-06

Participant Flow

As prespecified in the protocol, the safety and pharmacokinetic (PK) data from Part 1 of the study, comparing participants with moderate hepatic impairment to healthy participants, were reviewed after completion of Part 1. Per protocol, a decision was made to not conduct Part 2 of the study, comparing participants with mild hepatic impairment to healthy participants.

Participant milestones

Participant milestones
Measure	Moderate Hepatic Impairment Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1.	Healthy Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.
Overall Study STARTED	7	7
Overall Study COMPLETED	7	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Moderate Hepatic Impairment Participants n=7 Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1.	Healthy Participants n=7 Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.	Total n=14 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 8.2 • n=5 Participants	57.1 Years STANDARD_DEVIATION 8.0 • n=7 Participants	56.4 Years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

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)

Population: All participants who were compliant with the study procedures and have available data from at least one treatment.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment Participants n=7 Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1.	Healthy Participants n=7 Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189	5600 h*nmol/L Interval 3020.0 to 10400.0	4710 h*nmol/L Interval 3340.0 to 6660.0

PRIMARY outcome

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)

Population: All participants who were compliant with the study procedures and have available data from at least one treatment

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.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment Participants n=7 Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1.	Healthy Participants n=7 Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.
Maximum Observed Plasma Concentration (Cmax) of MK-8189	194 nmol/L Interval 127.0 to 296.0	158 nmol/L Interval 131.0 to 191.0

SECONDARY outcome

Timeframe: Up to approximately 15 days

Population: All participants who received at least one dose of treatment

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.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment Participants n=7 Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1.	Healthy Participants n=7 Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.
Number of Participants Who Experience One or More Adverse Events (AEs)	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 15 days

Population: All participants who received at least one dose of treatment

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment Participants n=7 Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1.	Healthy Participants n=7 Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.
Number of Participants Who Discontinue From the Study Due to an AE	0 Participants	0 Participants

Adverse Events

Moderate Hepatic Impairment Participants

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Healthy Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Moderate Hepatic Impairment Participants n=7 participants at risk Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1	Healthy Participants n=7 participants at risk Healthy participants received a single dose of MK-8189 4 mg orally on Day 1.
Gastrointestinal disorders Vomiting	28.6% 2/7 • Number of events 2 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Injury, poisoning and procedural complications Fall	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Metabolism and nutrition disorders Decreased appetite	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Musculoskeletal and connective tissue disorders Muscle spasms	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Nervous system disorders Dizziness	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Nervous system disorders Headache	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Psychiatric disorders Affect lability	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Psychiatric disorders Anxiety	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Vascular disorders Hot flush	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included
Vascular disorders Hypotension	14.3% 1/7 • Number of events 1 • Up to approximately 15 days All participants who received at least one dose of treatment are included	0.00% 0/7 • Up to approximately 15 days All participants who received at least one dose of treatment are included

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments
Publication restrictions are in place

Restriction type: OTHER