Islatravir and Methadone Pharmacokinetics (MK-8591-029)

• Status: Completed
• Trial end date: 2021-07-09
• Target enrollment: 0
• Participant gender: All

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 single-dose co-administration of methadone + ISL.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Islatravir; Methadone

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

• 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

• With the exception of tetrahydrocannabinol (THC), has a positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines (with the exception noted in exclusion criteria 7), or opiates/opioids on Day -1

• 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