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

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04994522
• Other study ID #: 6482-021
• Secondary ID: MK-6482-021
• Status: Completed
• Phase: Phase 1
• Start date: July 12, 2022
• Est. completion date: April 11, 2024

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 11, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Belzutifan
Three 40 mg tablets given as a single oral 120 mg dose.

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center ( Site 0001)	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information