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

Study Overview
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Brief Summary
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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.

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

Conditions
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End Stage Renal Disease, Renal Impairment

Intervention / Treatment
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* Drug: Belzutifan


Participation Criteria
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Eligibility Criteria
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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 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 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belzutifan in Participants with ESRD<br>Participants with ESRD will receive a single dose of belzutifan 120 mg orally on Day 1 of a 4-day treatment period (Period 1), followed by a ≥7 day washout period. Participants receive another single dose of belzutifan 120 mg orally on Day 1 of a 4-day treatment period (Period 2). | Drug: Belzutifan<br>* Three 40 mg tablets given as a single oral 120 mg dose.<br>* Other names: WELIREG;|
| Experimental: Belzutifan in Healthy Participants<br>Participants in the healthy matched control group will receive a single dose of belzutifan 120 mg orally on Day 1 of a 4-day treatment period (Period 1). | Drug: Belzutifan<br>* Three 40 mg tablets given as a single oral 120 mg dose.<br>* Other names: WELIREG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration time curve of belzutifan from hour 0 to infinity (AUC0-inf) | Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC0-inf of belzutifan. | 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) | Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC0-24 of belzutifan. | 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 | Blood samples collected predose and at multiple timepoints postdose will be used to determine 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 | 
| Time to maximum plasma concentration (Tmax) of belzutifan | Blood samples collected predose and at multiple timepoints postdose will be used to determine 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 | 
| Apparent terminal half-life (t½) of plasma belzutifan | Blood samples collected predose and at multiple timepoints postdose will be used to determine the apparent terminal t1/2 of belzutifan. | Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dialysis clearance of belzutifan based on plasma (CLD, plasma) | Blood samples collected at pre-dialysis and at multiple timepoints post-dialysis will be used to measure the extent of belzutifan removal by HD. | 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) | 
| Number of participants who experienced an adverse event (AE) | 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 number of participants who experienced an AE will be reported. | Up to approximately 29 days | 
| Number of participants who discontinued from the study due to an AE | 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 number of participants who discontinued the study due to an AE will be reported. | Up to approximately 29 days |