NCT04568603

Islatravir and Methadone Pharmacokinetics (MK-8591-029)

Completed Phase 1 Results posted Last updated 28 January 2025

What this trial tests

Phase 1 trial testing Islatravir in HIV-1 Infection in 14 participants. Completed in 9 July 2021.

Timeline

16 October 2020

Primary endpoint
9 July 2021

9 July 2021

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	14
Start date	16 October 2020
Primary completion	9 July 2021
Estimated completion	9 July 2021
Sites	2 locations across United States

Drugs / interventions tested

• Islatravir — full drug profile →

Conditions studied

• HIV-1 Infection — all drugs for HIV-1 Infection →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 65, any sex, with HIV-1 Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone Primary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The AUC0-24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	61.9	49.3 – 77.7

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	63.9	52.2 – 78.1

Dose-Normalized AUC0-24 of S-Methadone Primary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The AUC0-24hr of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	63.1	48.9 – 81.5

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	65.1	51.7 – 82.0

Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The Cmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	3.64	3.00 – 4.43

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	3.71	3.14 – 4.40

Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone Secondary · Days 1 and 2: 24 hours postdose

The C24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	2.09	1.63 – 2.69

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	2.23	1.78 – 2.78

Time to Maximum Plasma Concentration (Tmax) of R-Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The Tmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	2.00	1.47 – 3.00

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	2.00	0.67 – 4.00

Dose-Normalized Cmax of S-Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The Cmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	4.25	3.45 – 5.25

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	4.31	3.49 – 5.32

Dose-Normalized C24 of S-Methadone Secondary · Days 1 and 2: 24 hours postdose

The C24 of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	1.91	1.44 – 2.54

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	2.07	1.60 – 2.68

Tmax of S-Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The Tmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	1.50	1.02 – 3.00

Day 2:Methadone + ISL

Group	Value	95% CI
Methadone + ISL	2.00	0.67 – 3.00

Dose-Normalized AUC0-24 of Total Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The AUC0-24hr of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	126	99.1 – 159

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	129	105 – 160

Dose-Normalized Cmax of Total Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The Cmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	7.91	6.48 – 9.66

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	8.02	6.64 – 9.68

Dose-Normalized C24 of Total Methadone Secondary · Days 1 and 2: 24 hours postdose

The C24 of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	4.03	3.10 – 5.23

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	4.32	3.42 – 5.45

Tmax of Total Methadone Secondary · Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

The Tmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

Day 1: Methadone Alone

Group	Value	95% CI
Methadone + ISL	2.00	1.47 – 3.00

Day 2: Methadone + ISL

Group	Value	95% CI
Methadone + ISL	2.00	0.67 – 3.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Methadone + ISL

Serious: 0/14 (0%)

Deaths: 0/14

Other adverse events (8 terms — click to expand)

Reaction	System	Methadone + ISL
Increased appetite	Metabolism and nutrition disorders	—
Headache	Nervous system disorders	—
Vomiting	Gastrointestinal disorders	—
Infusion site extravasation	General disorders	—
Anxiety	Psychiatric disorders	—
Nightmare	Psychiatric disorders	—
Papule	Skin and subcutaneous tissue disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—

Data from ClinicalTrials.gov NCT04568603 adverse events section.

Sponsor's own description

The present study is designed to determine the effect of islatravir (ISL) \[MK-8591\] on methadone pharmacokinetics (PK). The primary objective is to assess whether ISL impacts the area under the plasma concentration time curve from dosing to 24 hours postdose (AUC0-24) of S-methadone and R-methadone in participants on oral methadone therapy. It is hypothesized that the plasma AUC0-24hr for S- and R-methadone will be similar after methadone alone compared to methadone and ISL 60 mg coadministration.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy.
   Matthews RP, Ankrom W, Handy W, Patel M, et al · · 2025 · cited 1× · PMID 39648614 · DOI 10.1002/cpdd.1492