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

NCT04515641 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 8591-030MK-8591-030
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (7)

• Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

• Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

• Maximum Concentration (Cmax) of ISL in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

• Time to Maximum Concentration (Tmax) of ISL in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median.

  Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

• Apparent Terminal Half-Life (t½) of ISL in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

  Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

• Apparent Total Clearance (CL/F) of ISL in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

  Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

• Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

  Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose

Secondary Outcomes (10)

• Percentage of Participants With an Adverse Event (AE)

  Up to 28 days

• Percentage of Participants Who Discontinued From the Study Due to an AE

  Up to 28 days

• AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC)

  Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

• AUC0-last of ISL-TP in PBMC

  Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

• Cmax of ISL-TP in PBMC

  Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose

Study Arms (2)

Moderate Hepatic Impairment

EXPERIMENTAL

Participants receive a single dose of ISL 60 mg.

Drug: Islatravir

Healthy Controls

EXPERIMENTAL

Participants receive a single dose of ISL 60 mg.

Drug: Islatravir

Interventions

Islatravir DRUG

Two ISL 30 mg capsules taken by mouth.

Also known as: MK-8591

Healthy Controls; Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Clinical Pharmacology of Miami ( Site 0001)

Miami, Florida, 33014, United States

Location

Related Publications (1)

• 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.

  PMID: 40042304 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

islatravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 17, 2020
• Study Start: November 5, 2020
• Primary Completion: September 13, 2021
• Study Completion: September 13, 2021
• Last Updated: July 17, 2025
• Results First Posted: July 3, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)