islatravir and methadone pharmacokinetics (mk-8591-029)

Conditions: HIV-1 Infection

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.


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 * 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