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

NCT04995484 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 6482-020MK-6482-020
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Moderate Hepatic Impairment

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (2)

• Number of Participants Who Experience an Adverse Event (AE)

  Up to 15 days

• Number of Participants Who Discontinue Study Treatment Due to an AE

  Up to 15 days

Study Arms (2)

Moderate Hepatic Impairment

EXPERIMENTAL

Participants with moderate hepatic impairment will receive a single oral 80 mg dose of belzutifan on Day 1.

Drug: Belzutifan

Healthy

EXPERIMENTAL

Participants with normal hepatic function will receive a single oral 80 mg dose of belzutifan on Day 1.

Drug: Belzutifan

Interventions

Belzutifan DRUG

Two 40 mg tablets given as a single oral 80 mg dose.

Also known as: MK-6482, PT2977, WELIREG

Healthy; Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Orlando Clinical Research Center ( Site 0001)

Orlando, Florida, 32809, United States

Location

The Texas Liver Institute ( Site 0002)

San Antonio, Texas, 78215, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

belzutifan

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Group

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 9, 2021
• Study Start: June 24, 2022
• Primary Completion: December 25, 2023
• Study Completion: January 3, 2024
• Last Updated: January 13, 2025
• Results First Posted: January 13, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (2)