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

Moderate Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04995484
• Other study ID #: 6482-020
• Secondary ID: MK-6482-020
• Status: Completed
• Phase: Phase 1
• Start date: June 24, 2022
• Est. completion date: January 3, 2024

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 3, 2024
• Est. primary completion date: December 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Liver Diseases
• Moderate Hepatic Impairment

Intervention

Drug:
• Belzutifan
Two 40 mg tablets given as a single oral 80 mg dose.

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center ( Site 0001)	Orlando	Florida
United States	The Texas Liver Institute ( Site 0002)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration time curve from hour 0 to infinity (AUC0-inf)	Blood samples collected prior to dose and at multiple timepoints postdose will be used to determine AUC0 to infinity of belzutifan.	Prior to dose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Primary	Area under the plasma concentration time curve from hour 0 to 24 (AUC0-24)	Blood samples collected prior to dose and at multiple timepoints postdose will be used to determine AUC0 to 24 hours of belzutifan.	Prior to dose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24 hours postdose
Primary	Maximum plasma concentration (Cmax)	Blood samples collected prior to dose and at multiple timepoints postdose will be used to determine Cmax of belzutifan.	Prior to dose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Primary	Time to maximum plasma concentration (Tmax)	Blood samples collected prior to dose and at multiple timepoints postdose will be used to determine the Tmax of belzutifan.	Prior to dose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Primary	Apparent terminal half-life (t½) of plasma concentration	Blood samples will be used to determine the apparent terminal t1/2 of belzutifan.	Prior to dose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose
Secondary	Number of participants who experienced an adverse event	An adverse event (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 adverse event. The number of participants who experienced an AE will be reported.	Up to 15 days
Secondary	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 adverse event. The number of participants who discontinued the study due to an AE will be reported.	Up to 15 days

External Links

•   Merck Clinical Trials Information