Islatravir and Methadone Pharmacokinetics (MK-8591-029)

NCT04568603 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 8591-029MK-8591-029
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (2)

• Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone

  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.

  Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

• Dose-Normalized AUC0-24 of S-Methadone

  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.

  Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

Secondary Outcomes (12)

• Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone

  Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

• Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone

  Days 1 and 2: 24 hours postdose

• Time to Maximum Plasma Concentration (Tmax) of R-Methadone

  Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

• Dose-Normalized Cmax of S-Methadone

  Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

• Dose-Normalized C24 of S-Methadone

  Days 1 and 2: 24 hours postdose

Study Arms (1)

Methadone + ISL

EXPERIMENTAL

Methadone-maintained participants (20 to 200 mg \[locally-provided\] once daily \[QD\] from Day -14 to Day -1 and Day 10 to Day 15) receive methadone 20 to 200 mg QD on Day 1 to Day 9; ISL 60 mg is co-administered with methadone on Day 2.

Drug: Islatravir

Interventions

Islatravir DRUG

ISL 30 mg x 2 (60 mg total) capsules taken by mouth.

Also known as: MK-8591

Methadone + ISL

Eligibility Criteria

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

You may qualify if:

• Has a body mass index (BMI) \> 18 and ≤ 35 kg/m\^2
• Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of study drug
• Is in good health based on medical history, physical examination, vital sign measurements, and electrocardiograms (ECGs) performed prior to randomization.
• Has a negative human immunodeficiency virus (HIV) antigen/antibody test at screening
• For male participants, follows contraception guidance consistent with local regulations
• For female participants:
• Is not a woman of childbearing potential (WOCBP) or
• Is a WOCBP and using acceptable contraception or is abstinent
• Is reliably participating in a methadone maintenance program for at least two (2) months prior to Day 1
• Agrees to not change their current maintenance methadone dose of 20-200 mg administered as a single daily dose

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 (eg, food, drug, latex) or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the screening visit
• With the exception of methadone, is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to the first dose of the 14-day methadone maintenance run-in phase prior to Day 1, throughout the trial, until the AE follow-up call (Day 16)
• Has participated in another investigational study within 4 weeks (or 5 half-lives) prior to the prestudy (screening) visit.
• Has a QTc interval \>450 msec (males) or \>470 msec (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 other than methadone
• Does not limit smoking to no more than 10 cigarettes per day while in the clinical research unit (CRU)
• Consumes greater than 3 glasses of alcoholic beverages per day
• Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
• Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Research Centers of America, LLC ( Site 0002)

Hollywood, Florida, 33024, United States

Location

PRA Health Sciences ( Site 0001)

Salt Lake City, Utah, 84124, United States

Location

Related Publications (1)

• Matthews RP, Ankrom W, Handy W, Patel M, Matthews C, Xu Z, Gravesande K, Searle S, Schwartz H, Stoch SA, Iwamoto M. A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy. Clin Pharmacol Drug Dev. 2025 Jan;14(1):36-43. doi: 10.1002/cpdd.1492. Epub 2024 Dec 8.

  PMID: 39648614 RESULT

MeSH Terms

Interventions

islatravir

Results Point of Contact

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

ClinicalTrialsDisclosure@msd.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: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: September 29, 2020
• Study Start: October 16, 2020
• Primary Completion: July 9, 2021
• Study Completion: July 9, 2021
• Last Updated: January 28, 2025
• Results First Posted: December 11, 2023

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (2)