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

NCT04994522 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 6482-021MK-6482-021
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

End Stage Renal Disease; Renal Impairment

Outcome Measures

Primary Outcomes (5)

• Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to Infinity (AUC0-inf)

  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.

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

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

  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.

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

• Maximum Plasma Concentration (Cmax) of Belzutifan

  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.

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

• Time to Maximum Plasma Concentration (Tmax) of Belzutifan

  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.

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

• 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.

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

Secondary Outcomes (3)

• 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)

• Percentage of Participants Who Experienced an Adverse Event (AE)

  Up to 32 days

• Percentage of Participants Who Discontinue Study Intervention Due to an AE

  Up to 12 days

Study Arms (2)

Belzutifan in Participants with ESRD

EXPERIMENTAL

In period 1, participants with ESRD will receive a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD will receive a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.

Drug: Belzutifan

Belzutifan in Healthy Participants

EXPERIMENTAL

In period 1, healthy participants will receive a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.

Drug: Belzutifan

Interventions

Belzutifan DRUG

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

Also known as: MK-6482, PT2977, WELIREG

Belzutifan in Healthy Participants; Belzutifan in Participants with ESRD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Orlando Clinical Research Center ( Site 0001)

Orlando, Florida, 32809, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 6, 2021
• Study Start: July 12, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 11, 2024
• Last Updated: April 6, 2025
• Results First Posted: April 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)