Clinical trial NCT04994522: A Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021)
Official title: An Open-Label, Single-Dose Study to Investigate the Influence of Renal Impairment on the Pharmacokinetics of MK-6482
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End Stage Renal Disease
Renal Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to Infinity (AUC0-inf)
timeFrame: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
measure: Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to 24 (AUC0-24)
timeFrame: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, and 24 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Belzutifan
timeFrame: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of Belzutifan
timeFrame: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
measure: Apparent Terminal Half-life (t½) of Plasma Belzutifan
timeFrame: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Secondary outcomes:
measure: Dialysis Clearance of Belzutifan Based on Plasma (CLD, Plasma)
timeFrame: 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)
measure: Percentage of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to 32 days
measure: Percentage of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to 12 days
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0001)
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: