Belzutifan (MK-6482) Hepatic Impairment Study (MK-6482-020)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Moderate Hepatic Impairment

Treatments: Drug: Belzutifan

Study type: Interventional

Funder types: Industry

Identifiers

NCT04995484

MK-6482-020 (Other Identifier)

6482-020

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

For Participants With Normal Hepatic Function

• Is in good health.
• Has a body mass index (BMI) 18.0-40.0 kg/m².

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

• With exception of the hepatic impairment, is in good health.
• Has a BMI 18.0-40.0 kg/m2.
• 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.

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

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, 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.

Other Exclusions

• Is a heavy smoker or heavy user of nicotine-containing products (>20 cigarettes or equivalent/day).
• Consumes greater than 3 glasses of alcoholic beverages 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 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.

Other Exclusions

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 2 patient groups

Belzutifan in participants with moderate hepatic impairment

Experimental group

Description:

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

Treatment:

Drug: Belzutifan

Belzutifan in participants with normal hepatic function

Experimental group

Description:

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

Treatment:

Drug: Belzutifan