NCT04994522

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

Completed Phase 1 Results posted Last updated 6 April 2025

What this trial tests

Phase 1 trial testing Belzutifan in End Stage Renal Disease in 14 participants. Completed in 11 April 2024.

Timeline

12 July 2022

Primary endpoint
1 April 2024

11 April 2024

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	12 July 2022
Primary completion	1 April 2024
Estimated completion	11 April 2024
Sites	1 location across United States

Drugs / interventions tested

• Belzutifan (BELZUTIFAN) — full drug profile →

Conditions studied

• End Stage Renal Disease — all drugs for End Stage Renal Disease →
• Renal Impairment — all drugs for Renal Impairment →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with End Stage Renal Disease or Renal 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 of Belzutifan From Hour 0 to Infinity (AUC0-inf) Primary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	17100	± 91.3
Belzutifan in ESRD After HD (Period 1)	21100	± 91.3
Belzutifan in Healthy Participants	18500	± 41.4

Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to 24 (AUC0-24) Primary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	10700	± 50.5
Belzutifan in Participants With ESRD After HD (Period 1)	12300	± 50.7
Belzutifan in Healthy Participants	13200	± 30.7

Maximum Plasma Concentration (Cmax) of Belzutifan Primary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	1110	± 44.0
Belzutifan in Participants With ESRD After HD (Period 1)	907	± 46.7
Belzutifan in Healthy Participants	1300	± 26.1

Time to Maximum Plasma Concentration (Tmax) of Belzutifan Primary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	2.00	1.00 – 3.00
Belzutifan in Participants With ESRD After HD (Period 1)	4.00	1.50 – 9.00
Belzutifan in Healthy Participants	1.00	0.50 – 3.00

Apparent Terminal Half-life (t½) of Plasma Belzutifan Primary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	15.1	± 68.1
Belzutifan in Participants With ESRD After HD (Period 1)	17.1	± 57.6
Belzutifan in Healthy Participants	13.9	± 20.9

Dialysis Clearance of Belzutifan Based on Plasma (CLD, Plasma) Secondary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	78.4	± 53.5

Percentage of Participants Who Experienced an Adverse Event (AE) Secondary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	14.3
Belzutifan in Participants With ESRD After HD (Period 1)	0.0
Belzutifan in Healthy Participants	16.7

Percentage of Participants Who Discontinue Study Intervention Due to an AE Secondary · 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.

Group	Value	95% CI
Belzutifan in Participants With ESRD Before HD (Period 2)	0.0
Belzutifan in Participants With ESRD After HD (Period 1)	0.0
Belzutifan in Healthy Participants	0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 32 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Belzutifan in Participants With ESRD Before HD (Period 2)

Serious: 1/7 (14%)

Deaths: 0/7

Belzutifan in Participants With ESRD After HD (Period 2)

Serious: 0/8 (0%)

Deaths: 0/8

Belzutifan in Healthy Participants

Serious: 0/6 (0%)

Deaths: 0/6

Serious adverse events (1 terms)

Reaction	System	Belzutifan in Participants…	Belzutifan in Participants…	Belzutifan in Healthy Part…
Bacteraemia	Infections and infestations	—	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Belzutifan in Participants…	Belzutifan in Participants…	Belzutifan in Healthy Part…
Headache	Nervous system disorders	—	—	—

Most-reported serious reactions: Bacteraemia.

Data from ClinicalTrials.gov NCT04994522 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.
   Chen Z, Han F, Du Y, Shi H, et al · · 2023 · cited 913× · PMID 36797231 · DOI 10.1038/s41392-023-01332-8
2. Belzutifan: a novel therapeutic for the management of von Hippel-Lindau disease and beyond.
   Curry L, Soleimani M. · · 2024 · cited 20× · PMID 38639572 · DOI 10.2217/fon-2023-0679