---
title: Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030)
nct_id: NCT04515641
overall_status: COMPLETED
phase: PHASE1
sponsor: Merck Sharp & Dohme LLC
study_type: INTERVENTIONAL
primary_condition: Human Immunodeficiency Virus (HIV) Infection
countries: United States
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT04515641.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT04515641"
ct_last_update_post_date: 2025-07-17
last_seen_at: "2026-05-12T07:06:47.085Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030)

**Official Title:** An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of Islatravir (MK-8591) in Participants With Moderate Hepatic Impairment

**NCT ID:** [NCT04515641](https://clinicaltrials.gov/study/NCT04515641)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE1
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 12
- **Lead Sponsor:** Merck Sharp & Dohme LLC
- **Conditions:** Human Immunodeficiency Virus (HIV) Infection
- **Start Date:** 2020-11-05
- **Completion Date:** 2021-09-13
- **CT.gov Last Update:** 2025-07-17

## 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.

## Eligibility

- **Minimum age:** 18 Years
- **Maximum age:** 75 Years
- **Sex:** ALL
- **Healthy Volunteers:** Yes

```
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
```

## Arms

- **Moderate Hepatic Impairment** (EXPERIMENTAL) — Participants receive a single dose of ISL 60 mg.
- **Healthy Controls** (EXPERIMENTAL) — Participants receive a single dose of ISL 60 mg.

## Interventions

- **Islatravir** (DRUG) — Two ISL 30 mg capsules taken by mouth.

## Primary Outcomes

- **Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma** _(time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.
- **Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma** _(time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.
- **Maximum Concentration (Cmax) of ISL in Plasma** _(time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.
- **Time to Maximum Concentration (Tmax) of ISL in Plasma** _(time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.
- **Apparent Terminal Half-Life (t½) of ISL in Plasma** _(time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.
- **Apparent Total Clearance (CL/F) of ISL in Plasma** _(time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.
- **Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma** _(time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose)_ — 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.

## Secondary Outcomes

- **Percentage of Participants With an Adverse Event (AE)** _(time frame: Up to 28 days)_
- **Percentage of Participants Who Discontinued From the Study Due to an AE** _(time frame: Up to 28 days)_
- **AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC)** _(time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose)_
- **AUC0-last of ISL-TP in PBMC** _(time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose)_
- **Cmax of ISL-TP in PBMC** _(time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose)_
- **Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC** _(time frame: 24 hours post-dose)_
- **Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC** _(time frame: 168 hours post-dose)_
- **Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC** _(time frame: 672 hours post-dose)_
- **Tmax of ISL-TP in PBMC** _(time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose)_
- **T1/2 of ISL-TP in PBMC** _(time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose)_

## Locations (1)

- Clinical Pharmacology of Miami ( Site 0001), Miami, Florida, United States

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.maxAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.clinical pharmacology of miami ( site 0001)|miami|florida|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT04515641.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT04515641*  
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