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

NCT ID: NCT04515641

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-05
• Study Completion Date: 2021-09-13

Brief Summary

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.

Conditions

Human Immunodeficiency Virus (HIV) Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Moderate Hepatic Impairment

Participants receive a single dose of ISL 60 mg.

Group Type: EXPERIMENTAL

Islatravir

Intervention Type: DRUG

Two ISL 30 mg capsules taken by mouth.

Healthy Controls

Participants receive a single dose of ISL 60 mg.

Group Type: EXPERIMENTAL

Islatravir

Intervention Type: DRUG

Two ISL 30 mg capsules taken by mouth.

Interventions

Islatravir

Two ISL 30 mg capsules taken by mouth.

Intervention Type: DRUG

Other Intervention Names

MK-8591

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Clinical Pharmacology of Miami ( Site 0001)

Miami, Florida, United States

Countries

United States

References

Matthews RP, Patel M, Liu W, Liu Y, Rondon JC, Vargo RC, Stoch SA, Iwamoto M. Pharmacokinetics of islatravir in participants with moderate hepatic impairment. Antimicrob Agents Chemother. 2025 Apr 2;69(4):e0155324. doi: 10.1128/aac.01553-24. Epub 2025 Mar 5.

Reference Type: RESULT

PMID: 40042304 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-8591-030

Identifier Type: OTHER

Identifier Source: secondary_id

8591-030

Identifier Type: -

Identifier Source: org_study_id