Islatravir and Methadone Pharmacokinetics (MK-8591-029)
Condition: HIV-1 Infection
Intervention: Islatravir
Intervention description: ISL 30 mg x 2 (60 mg total) capsules taken by mouth.
Intervention MeSH terms: Islatravir
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

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