Trial Outcomes & Findings for A Study of Belzutifan (MK-6482) in Participants With Hepatic Impairment (MK-6482-020) (NCT NCT04995484)

Last Updated: 2025-01-13

Results Overview

Cmax was defined as the peak level belzutifan reaches in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose

Results posted on

2025-01-13

Participant Flow

Participant milestones

Participant milestones
Measure	Moderate Hepatic Impairment Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Overall Study STARTED	9	8
Overall Study COMPLETED	9	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Belzutifan (MK-6482) in Participants With Hepatic Impairment (MK-6482-020)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.	Total n=17 Participants Total of all reporting groups
Age, Continuous	60.7 Years STANDARD_DEVIATION 2.69 • n=5 Participants	61.4 Years STANDARD_DEVIATION 5.63 • n=7 Participants	61.0 Years STANDARD_DEVIATION 4.20 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	5 Participants n=7 Participants	12 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	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	6 Participants n=7 Participants	15 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: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose

Population: All participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, who have available measurement data, and have no important protocol deviations.

AUC0-Inf was defined as the area under the concentration-time curve of belzutifan from time zero to infinity. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0-Inf of belzutifan.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Belzutifan	22500 ng*hr/mL Geometric Coefficient of Variation 80.3	14800 ng*hr/mL Geometric Coefficient of Variation 35.1

PRIMARY outcome

Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24 hours postdose

AUC0-24hrs was defined as the area under the concentration-time curve of belzutifan from time zero to 24 hours postdose. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0 to 24 hours of belzutifan.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24hrs) of Belzutifan	10500 ng*hr/mL Geometric Coefficient of Variation 34.5	9650 ng*hr/mL Geometric Coefficient of Variation 28.8

PRIMARY outcome

Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose

Cmax was defined as the peak level belzutifan reaches in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Maximum Plasma Concentration (Cmax) of Belzutifan	852 ng/mL Geometric Coefficient of Variation 28.7	870 ng/mL Geometric Coefficient of Variation 31.4

PRIMARY outcome

Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose

Tmax was defined as the time it took belzutifan to reach its peak level in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine the Tmax of belzutifan.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Time to Maximum Plasma Concentration (Tmax) of Belzutifan	2.00 hr Interval 0.5 to 3.0	2.00 hr Interval 1.0 to 3.0

PRIMARY outcome

Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose

Apparent terminal half-life (t1/2) was defined as the time needed to reduce the level of belzutifan in the blood by one-half (1/2). Blood samples collected predose and at multiple timepoints postdose were used to determine the apparent terminal half-life (t1/2) of belzutifan.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Apparent Terminal Half-life (t1/2) of Belzutifan	23.5 hr Geometric Coefficient of Variation 70.5	15.4 hr Geometric Coefficient of Variation 16.4

SECONDARY outcome

Timeframe: Up to 15 days

Population: All participants who were allocated and received study treatment.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is reported.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Number of Participants Who Experience an Adverse Event (AE)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 15 days

Population: All participants who were allocated and received study treatment.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment n=9 Participants Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy n=8 Participants Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Number of Participants Who Discontinue Study Treatment Due to an AE	0 Participants	0 Participants

Adverse Events

Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Healthy Matched Control

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Moderate Hepatic Impairment n=9 participants at risk Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1.	Healthy Matched Control n=8 participants at risk Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1.
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Number of events 1 • Up to 15 days All Cause Mortality is reported for all allocated participants. Serious Adverse Events and Other Adverse Events are reported for all participants who received treatment.	0.00% 0/8 • Up to 15 days All Cause Mortality is reported for all allocated participants. Serious Adverse Events and Other Adverse Events are reported for all participants who received treatment.
Nervous system disorders Headache	0.00% 0/9 • Up to 15 days All Cause Mortality is reported for all allocated participants. Serious Adverse Events and Other Adverse Events are reported for all participants who received treatment.	12.5% 1/8 • Number of events 1 • Up to 15 days All Cause Mortality is reported for all allocated participants. Serious Adverse Events and Other Adverse Events are reported for all participants who received treatment.

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 The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. A coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.
Publication restrictions are in place

Restriction type: OTHER