A Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021)

An Open-Label, Single-Dose Study to Investigate the Influence of Renal Impairment on the Pharmacokinetics of MK-6482

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04994522

Enrollment

Registered

2021-08-06

Start date

2022-07-12

Completion date

2024-04-11

Last updated

2025-04-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

End Stage Renal Disease, Renal Impairment

Brief summary

The primary purpose of this study is to compare the plasma pharmacokinetics (PK) of belzutifan (MK-6482) following a single oral 120 mg dose in participants with end stage renal disease (ESRD) before and after hemodialysis (HD) to each other and also to that of healthy matched control participants. This study will also evaluate the safety and tolerability of a single oral 120 mg dose of belzutifan in participants with ESRD and the extent of belzutifan removed by HD.

Interventions

DRUGBelzutifan

Three 40 mg tablets given as a single oral 120 mg dose.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

Inclusion criteria

For Participants With Healthy Renal Function * Is in good health based on the opinion of the investigator. * Male participants agree to remain abstinent from heterosexual intercourse on a long-term basis or must agree to use contraception as instructed. * Female participants must be of nonchildbearing potential. For Participants With end stage renal disease (ESRD) * With exception of the renal impairment, is in good health based on the opinion of the investigator. * Has ESRD maintained on stable regimen of at least 3 times per week hemodialysis (HD) for at least 3 months prior to the initial administration of the study intervention. * Male participants agree to remain abstinent from heterosexual intercourse on a long-term basis or must agree to use contraception as instructed. * Female participants must be of nonchildbearing potential.

Exclusion criteria

For Participants With Healthy Renal Function * Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. * Has a history of cancer (malignancy). * Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV). * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. * Has received any non-live vaccine starting from 14 days prior to study intervention or is scheduled to receive any non-live vaccine through 30 days following study intervention (except coronavirus disease 2019 \[COVID-19\]). Participants With ESRD * Has a history of cancer (malignancy). * Has required frequent emergent HD (≥3) within a year prior to the initial dose of study intervention. * Is positive for HBsAg, hepatitis C antibodies, or HIV. * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. * Has received any non-live vaccine starting from 14 days prior to study intervention or is scheduled to receive any non-live vaccine through 30 days following study intervention (except COVID-19)

Design outcomes

Primary

Measure	Time frame	Description
Apparent Terminal Half-life (t½) of Plasma Belzutifan	Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose	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.
Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to 24 (AUC0-24)	Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, and 24 hours postdose	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.
Maximum Plasma Concentration (Cmax) of Belzutifan	Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose	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.
Time to Maximum Plasma Concentration (Tmax) of Belzutifan	Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose	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.
Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to Infinity (AUC0-inf)	Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose	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.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Experienced an Adverse Event (AE)	Up to 32 days	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.
Percentage of Participants Who Discontinue Study Intervention Due to an AE	Up to 12 days	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.
Dialysis Clearance of Belzutifan Based on Plasma (CLD, Plasma)	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)	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.

Countries

United States

Participant flow

Recruitment details

Participants with end stage renal diseases (ESRD) and healthy matched control participants were recruited at a single study site in the United States.

Participants by arm

Arm	Count
Belzutifan in Participants With ESRD 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.	8
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.	6
Total	14

Baseline characteristics

Characteristic	Belzutifan in Healthy Participants	Total	Belzutifan in Participants With ESRD
Age, Continuous	55.5 Years STANDARD_DEVIATION 7.42	56.5 Years STANDARD_DEVIATION 7.79	57.3 Years STANDARD_DEVIATION 8.48
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	3 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	11 Participants	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	9 Participants	7 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	4 Participants	0 Participants
Sex: Female, Male Female	6 Participants	14 Participants	8 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 8	0 / 6
other Total, other adverse events	0 / 7	0 / 8	1 / 6
serious Total, serious adverse events	1 / 7	0 / 8	0 / 6

Outcome results

Primary

Apparent Terminal Half-life (t½) of Plasma Belzutifan

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.

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