Trial Outcomes & Findings for A Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021) (NCT NCT04994522)
NCT ID: NCT04994522
Last Updated: 2025-04-06
Results Overview
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 in plasma.
COMPLETED
PHASE1
14 participants
Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
2025-04-06
Participant Flow
Participants with end stage renal diseases (ESRD) and healthy matched control participants were recruited at a single study site in the United States.
Participant milestones
| Measure |
Belzutifan in Participants With ESRD
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after hemodialysis (HD). In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|
|
Period 1
STARTED
|
8
|
6
|
|
Period 1
COMPLETED
|
8
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
7
|
6
|
|
Period 2
COMPLETED
|
7
|
6
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021)
Baseline characteristics by cohort
| Measure |
Belzutifan in Participants With ESRD
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.3 Years
STANDARD_DEVIATION 8.48 • n=99 Participants
|
55.5 Years
STANDARD_DEVIATION 7.42 • n=107 Participants
|
56.5 Years
STANDARD_DEVIATION 7.79 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdosePopulation: All participants who are compliant with the study procedure and have available data considered sufficient to exhibit the effect of treatment.
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 in plasma.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to Infinity (AUC0-inf)
|
17100 ng•hr/mL
Geometric Coefficient of Variation 91.3
|
21100 ng•hr/mL
Geometric Coefficient of Variation 91.3
|
18500 ng•hr/mL
Geometric Coefficient of Variation 41.4
|
PRIMARY outcome
Timeframe: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, and 24 hours postdosePopulation: All participants who are compliant with the study procedure and have available data considered sufficient to exhibit the effect of treatment.
AUC0-24 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 AUC0-24 of belzutifan in plasma.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to 24 (AUC0-24)
|
10700 ng•hr/mL
Geometric Coefficient of Variation 50.5
|
12300 ng•hr/mL
Geometric Coefficient of Variation 50.7
|
13200 ng•hr/mL
Geometric Coefficient of Variation 30.7
|
PRIMARY outcome
Timeframe: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdosePopulation: All participants who are compliant with the study procedure and have available data considered sufficient to exhibit the effect of treatment.
Cmax is the maximum concentration of belzutifan observed in plasma. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan in plasma.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Belzutifan
|
1110 ng/mL
Geometric Coefficient of Variation 44.0
|
907 ng/mL
Geometric Coefficient of Variation 46.7
|
1300 ng/mL
Geometric Coefficient of Variation 26.1
|
PRIMARY outcome
Timeframe: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdosePopulation: All participants who are compliant with the study procedure and have available data considered sufficient to exhibit the effect of treatment.
Tmax is the amount of time that belzutifan is present at the maximum concentration observed in plasma. Blood samples collected predose and at multiple timepoints postdose were used to determine Tmax of belzutifan in plasma.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of Belzutifan
|
2.00 hour
Interval 1.0 to 3.0
|
4.00 hour
Interval 1.5 to 9.0
|
1.00 hour
Interval 0.5 to 3.0
|
PRIMARY outcome
Timeframe: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdosePopulation: All participants who are compliant with the study procedure and have available data considered sufficient to exhibit the effect of treatment.
t1/2 is defined as the time required to divide plasma concentration of belzutifan by half. Blood samples collected predose and at multiple timepoints postdose were used to determine the apparent terminal t1/2 of belzutifan in plasma.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Apparent Terminal Half-life (t½) of Plasma Belzutifan
|
15.1 hour
Geometric Coefficient of Variation 68.1
|
17.1 hour
Geometric Coefficient of Variation 57.6
|
13.9 hour
Geometric Coefficient of Variation 20.9
|
SECONDARY outcome
Timeframe: Pre-dialysis, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 hours post-dialysis on Day 1 of Period 2 (Study Day ~12)Population: Per protocol, CLD was measured in participants with ESRD who were treated with belzutifan before HD (Period 2). Participants in period 2 who are compliant with the study procedure and have available data considered sufficient to exhibit the effect of treatment.
CLD, plasma is defined as a measure of the extent of belzutifan removed by HD. Blood samples collected at pre-dialysis and at multiple timepoints post-dialysis were used to measure the extent of belzutifan in plasma removal by HD.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Dialysis Clearance of Belzutifan Based on Plasma (CLD, Plasma)
|
78.4 mL/min
Geometric Coefficient of Variation 53.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 32 daysPopulation: All participants who received at least one dose of study intervention.
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants who experienced an AE are reported.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced an Adverse Event (AE)
|
14.3 Percentage of Participants
|
0.0 Percentage of Participants
|
16.7 Percentage of Participants
|
SECONDARY outcome
Timeframe: Up to 12 daysPopulation: All participants who received at least one dose of study intervention.
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants who discontinue study intervention due to an AE are reported.
Outcome measures
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in ESRD After HD (Period 1)
n=8 Participants
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 Participants
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Percentage of Participants Who Discontinue Study Intervention Due to an AE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
Adverse Events
Belzutifan in Participants With ESRD Before HD (Period 2)
Belzutifan in Participants With ESRD After HD (Period 2)
Belzutifan in Healthy Participants
Serious adverse events
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 participants at risk
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Participants With ESRD After HD (Period 2)
n=8 participants at risk
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 participants at risk
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Infections and infestations
Bacteraemia
|
14.3%
1/7 • Number of events 1 • Up to 32 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. All adverse events that occurred after dosing are summarized. Every participant is counted a single time for each applicable adverse event.
|
0.00%
0/8 • Up to 32 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. All adverse events that occurred after dosing are summarized. Every participant is counted a single time for each applicable adverse event.
|
0.00%
0/6 • Up to 32 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. All adverse events that occurred after dosing are summarized. Every participant is counted a single time for each applicable adverse event.
|
Other adverse events
| Measure |
Belzutifan in Participants With ESRD Before HD (Period 2)
n=7 participants at risk
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Participants With ESRD After HD (Period 2)
n=8 participants at risk
In period 1, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD received a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
|
Belzutifan in Healthy Participants
n=6 participants at risk
In period 1, healthy participants received a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/7 • Up to 32 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. All adverse events that occurred after dosing are summarized. Every participant is counted a single time for each applicable adverse event.
|
0.00%
0/8 • Up to 32 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. All adverse events that occurred after dosing are summarized. Every participant is counted a single time for each applicable adverse event.
|
16.7%
1/6 • Number of events 1 • Up to 32 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. All adverse events that occurred after dosing are summarized. Every participant is counted a single time for each applicable adverse event.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
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. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors (ICMJE) authorship requirements.
- Publication restrictions are in place
Restriction type: OTHER