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

Phase 1

Completed

Conditions: Renal Impairment
End Stage Renal Disease

Interventions: Drug: Belzutifan

Registration Number: NCT04994522

Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Belzutifan in Participants with ESRD	Belzutifan	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.
Belzutifan in Healthy Participants	Belzutifan	In period 1, healthy participants will receive a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.

Primary Outcome Measures

Name	Time	Method
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.
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.
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.