Clinical trial NCT04995484: A Study of Belzutifan (MK-6482) in Participants With Hepatic Impairment (MK-6482-020)
Official title: An Open-Label, Single-Dose Study to Investigate the Influence of Hepatic Impairment on the Pharmacokinetics of MK-6482
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate Hepatic Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-08-09
Enrollment: 17
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
Intervention model description: Parallel Group
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Belzutifan
timeFrame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
measure: Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24hrs) of Belzutifan
timeFrame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 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, 72, 96, and 120 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, 72, 96, and 120 hours postdose
measure: Apparent Terminal Half-life (t1/2) of Belzutifan
timeFrame: 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:
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to 15 days
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to 15 days
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0001)
state: Florida
city: San Antonio
country: United States
facility: The Texas Liver Institute ( Site 0002)
state: Texas
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: