Back to resultsA Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021)
Primary Purpose
End Stage Renal Disease, Renal Impairment
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belzutifan
Sponsored by
About this trial
This is an interventional treatment trial for End Stage Renal Disease
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 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)
Sites / Locations
- Orlando Clinical Research Center ( Site 0001)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Belzutifan in Participants with ESRD
Belzutifan in Healthy Participants
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
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.
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.
Maximum plasma concentration (Cmax) of belzutifan
Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of belzutifan.
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.
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT04994522
First Posted
August 2, 2021
Last Updated
October 19, 2023
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT04994522
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 12, 2022 (Actual)
Primary Completion Date
December 21, 2023 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease, Renal Impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Belzutifan in Participants with ESRD
Arm Type
Experimental
Arm Description
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).
Arm Title
Belzutifan in Healthy Participants
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Belzutifan
Other Intervention Name(s)
MK-6482, PT2977, WELIREG
Intervention Description
Three 40 mg tablets given as a single oral 120 mg dose.
Primary Outcome Measure Information:
Title
Area under the plasma concentration time curve of belzutifan from hour 0 to infinity (AUC0-inf)
Description
Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC0-inf of belzutifan.
Time Frame
Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Title
Area under the plasma concentration time curve of belzutifan from hour 0 to 24 (AUC0-24)
Description
Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC0-24 of belzutifan.
Time Frame
Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, and 24 hours postdose
Title
Maximum plasma concentration (Cmax) of belzutifan
Description
Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of belzutifan.
Time Frame
Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Title
Time to maximum plasma concentration (Tmax) of belzutifan
Description
Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of belzutifan.
Time Frame
Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Title
Apparent terminal half-life (t½) of plasma belzutifan
Description
Blood samples collected predose and at multiple timepoints postdose will be used to determine the apparent terminal t1/2 of belzutifan.
Time Frame
Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Secondary Outcome Measure Information:
Title
Dialysis clearance of belzutifan based on plasma (CLD, plasma)
Description
Blood samples collected at pre-dialysis and at multiple timepoints post-dialysis will be used to measure the extent of belzutifan removal by HD.
Time Frame
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)
Title
Number of participants who experienced an adverse event (AE)
Description
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.
Time Frame
Up to approximately 29 days
Title
Number of participants who discontinued from the study due to an AE
Description
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.
Time Frame
Up to approximately 29 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Orlando Clinical Research Center ( Site 0001)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
407-472-0270
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information
Learn more about this trial
A Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021)
We'll reach out to this number within 24 hrs