Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Human Immunodeficiency Virus (HIV) Infection

Treatments: Drug: Islatravir

Study type: Interventional

Funder types: Industry

Identifiers

NCT04515641

MK-8591-030 (Other Identifier)

8591-030

Details and patient eligibility

About

This is an open-label, single-dose study of the plasma pharmacokinetics (PK), safety, and tolerability of islatravir (ISL, MK-8591), and the intracellular PK of ISL triphosphate (ISL-TP) in male and female adult participants with moderate hepatic impairment and in healthy matched control participants.

Enrollment: 12 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Healthy Control Participants:

• Is in good health based on medical history, physical examination, vital sign (VS) measurements and electrocardiograms (ECGs) performed prior to randomization
• Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of the initial dose of study drug.
• Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2

Hepatic Impairment Participants:

• Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
• Has a score on the Child-Pugh scale ranging from 7 to 9 (moderate hepatic insufficiency) at screening
• With the exception of hepatic impairment, is in generally good health
• Has a BMI ≥ 18.5 and ≤ 40 kg/m2

Healthy and Hepatic Impairment Participants:

• Males : uses contraception according to local regulations
• Females: is not pregnant or breastfeeding and one of the following applies:
• Is not a woman of childbearing potential (WOCBP) OR
• Is a WOCBP and uses an acceptable contraceptive method
• A WOCBP with negative highly sensitive pregnancy test within 24 hours of study intervention

Exclusion criteria

• 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 at the time of prestudy (screening) visit or expected during the conduct of the study 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, or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food
• Has known hypersensitivity to the active substance or any of the excipients of the study drug
• Is positive for hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or HIV-2
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
• Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to study drug administration, throughout the study, until the poststudy visit
• Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
• Has a QTc interval >470 for males or >480 ms for females, has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking concomitant medications that prolong the QT/QTc interval
• Is not considered low risk of having HIV infection
• Is a smoker or user of electronic cigarettes and/or has used nicotine or nicotine-containing products (eg, nicotine patch) within 3 months of screening
• Consumes greater than 3 glasses of alcoholic beverages per day
• Consumes more than 6 caffeinated beverages per day
• Is a regular user of illicit drugs or has a history of drug abuse within 2 years
• Presents any concern to the investigator regarding safe study participation
• Is unwilling to comply with study restrictions
• Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Moderate Hepatic Impairment

Experimental group

Description:

Participants receive a single dose of ISL 60 mg.

Treatment:

Drug: Islatravir

Healthy Controls

Experimental group

Description:

Participants receive a single dose of ISL 60 mg.

Treatment:

Drug: Islatravir