A Study of Belzutifan (MK-6482) in Participants With Hepatic Impairment (MK-6482-020)

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

The primary purpose of this study is to compare the plasma pharmacokinetics (PK) of belzutifan (MK-6482) following a single oral 80 mg dose of belzutifan in participants with moderate hepatic impairment to that of healthy matched control participants. This study will also evaluate the safety and tolerability of a single oral 80 mg dose of belzutifan in participants with moderate hepatic impairment.

Study Overview

• Status: Completed
• Conditions: Moderate Hepatic Impairment
• Intervention / Treatment: Drug: Belzutifan

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center ( Site 0001)
  • Texas
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute ( Site 0002)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All Participants:

• Is in good health.
• Has a body mass index (BMI) 18.0-40.0 kg/m^2.

For Participants With Normal Hepatic Function:

Male Participants -Must have been vasectomized or surgically sterilized for at least 4 months or more prior to study intervention administration and agree to the following during the intervention period and for at least 5 days after administration of study intervention, be abstinent from heterosexual intercourse as their preferred and usual lifestyle or must agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.

Female Participants

-Is a woman of non-childbearing potential (WONCBP).

For Participants With Moderate Hepatic Impairment

• Has a diagnosis of chronic (>6 months), stable (no acute episodes of illness within the previous 30 days from administration of study intervention due to deterioration in hepatic function) hepatic impairment.
• Has a score on the Child-Pugh scale of B (a score of 7-9 on Child-Pugh Score)

Male Participants -Have been vasectomized or surgically sterilized for at least 4 months or more prior to study intervention administration and agree to the following during the intervention period and for at least 5 days after administration of study intervention, be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.

Female Participants

- Must be a WONCBP.

Exclusion Criteria:

All Participants:

• Is a heavy smoker or heavy user of nicotine-containing products (>20 cigarettes or equivalent/day).
• Consumes greater than 3 glasses of alcoholic beverages or equivalent per day.
• Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day.
• Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within the last 2 years.
• Presents any concern by the investigator regarding safe participation in the study.

For Participants with Normal Hepatic Function

• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
• Is mentally or legally incapacitated, has significant emotional problems or has a history of clinically significant psychiatric disorder of the last 5 years.
• Has a history of cancer (malignancy).
• Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food.
• 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 within the last 4 weeks.
• Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs (with the exception of prescription drugs that are approved by the investigator and Sponsor) or herbal remedies for the prohibited period of time.
• Has received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention. Exception: COVID-19 vaccine may be administered.
• Has participated in another investigational study within 4 weeks prior to study intervention administration.

For Participants With Moderate Hepatic Impairment

• Is mentally or legally incapacitated, has significant emotional problems or has a history of clinically significant psychiatric disorder in the last 5 years.
• Has a history of cancer (malignancy).
• Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food.
• Has fluctuating or rapidly deteriorating hepatic function.
• Has a history of liver or other solid organ transplantation.
• Has transjugular intrahepatic portosystemic shunt and/or has undergone portacaval shunting.
• Has encephalopathy Grade 3 or worse within 28 days before administration of study intervention.
• Is positive for HIV.
• Has had major surgery, donated or lost 1 unit of blood within the last 4 weeks.
• Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs (with the exception of prescription drugs that are approved by the investigator and Sponsor) or herbal remedies for the prohibited period of time.
• Has received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention. Exception: COVID-19 vaccine may be administered.
• Has participated in another investigational study within 4 weeks prior to study intervention administration.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Hepatic Impairment; Participants with moderate hepatic impairment will receive a single oral 80 mg dose of belzutifan on Day 1.	Drug: Belzutifan; Two 40 mg tablets given as a single oral 80 mg dose.; Other Names: MK-6482; PT2977; WELIREG
Experimental: Healthy; Participants with normal hepatic function will receive a single oral 80 mg dose of belzutifan on Day 1.	Drug: Belzutifan; Two 40 mg tablets given as a single oral 80 mg dose.; Other Names: MK-6482; PT2977; WELIREG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Belzutifan	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.	Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24hrs) of Belzutifan	AUC0-24hrs 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 to 24 hours of belzutifan.	Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24 hours postdose
Maximum Plasma Concentration (Cmax) of Belzutifan	Cmax was defined as the peak level belzutifan reaches in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan.	Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Time to Maximum Plasma Concentration (Tmax) of Belzutifan	Tmax was defined as the time it took belzutifan to reach its peak level in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine the Tmax of belzutifan.	Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Apparent Terminal Half-life (t1/2) of Belzutifan	Apparent terminal half-life (t1/2) was defined as the time needed to reduce the level of belzutifan in the blood by one-half (1/2). Blood samples collected predose and at multiple timepoints postdose were used to determine the apparent terminal half-life (t1/2) of belzutifan.	Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is reported.	Up to 15 days
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued the study due to an AE is reported.	Up to 15 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2022
• Primary Completion (Actual): December 25, 2023
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Antineoplastic Agents; Belzutifan
• Other Study ID Numbers: 6482-020; MK-6482-020 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No