Islatravir and Methadone Pharmacokinetics (MK-8591-029)

NCT ID: NCT04568603

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-16
• Study Completion Date: 2021-07-09

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Methadone + ISL

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.

Group Type: EXPERIMENTAL

Islatravir

Intervention Type: DRUG

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

Interventions

Islatravir

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

Intervention Type: DRUG

Other Intervention Names

MK-8591

Eligibility Criteria

Inclusion Criteria

• 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

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 (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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 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

Research Centers of America, LLC ( Site 0002)

Hollywood, Florida, United States

PRA Health Sciences ( Site 0001)

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 39648614 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-8591-029

Identifier Type: OTHER

Identifier Source: secondary_id

8591-029

Identifier Type: -

Identifier Source: org_study_id