Effects of Doravirine (MK-1439) on Methadone Pharmacokinetics in Methadone-Maintained Participants (MK-1439-045)
Condition: Human Immunodeficiency Virus (HIV) Infection
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Methadone; Doravirine
Intervention description: Methadone 20 to 200 mg (10 mg/mL if oral solution concentrate) oral tablet once per day.; Doravirine 100 mg oral tablet once per day.
Intervention MeSH terms: Methadone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
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:

      This study will evaluate the effects of multiple doses of doravirine (MK-1439) on the
      pharmacokinetics of methadone in participants requiring methadone maintenance therapy. The
      primary hypothesis is that area under the plasma concentration-time curve to 24 hours
      postdose (AUC0-24) of (R)-methadone is similar when a maintenance regimen of methadone is
      administered with or without multiple daily doses of doravirine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  If female with reproductive potential: must demonstrate a serum β-human chorionic
             gonadotropin (β -hCG) level consistent with the nongravid state and agree to use
             (and/or have their partner use) two acceptable methods of birth control throughout the
             trial and until 2 weeks after the last dose of trial drug.

          -  If postmenopausal female: must be without menses for at least 1 year.

          -  If surgically sterile female: must have a status of post hysterectomy, oophorectomy or
             tubal ligation.

          -  Body Mass Index (BMI) of 18-35 kg/m^2 (inclusive).

          -  Able to comply with the smoking restrictions, including <=10 cigarettes per day while
             in the Clinical Research Unit, and no smoking from 2 hours predose to 2 hours postdose
             on Days 1 and 6.

          -  Reliably participating in a methadone maintenance program for at least two months
             prior to Day 1. Required to be on a documented stable dose of methadone for at least
             14 days prior to Day 1.

          -  Agree not to change current maintenance methadone dose of 20-200 mg once daily (unless
             for safety reasons) from screening until the end of the study. Must agree to
             observation and documentation of daily methadone dose administration during the period
             of the study during which they are domiciled.

        Exclusion Criteria:

          -  Mentally or legally incapacitated, have significant emotional problems at the time of
             pretrial (screening) visit or expected during the conduct of the trial or have a
             history of clinically significant psychiatric disorder of the last 5 years.
             Participants who have had situational depression may be enrolled in the trial at the
             discretion of the investigator.

          -  History of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, hepatic, immunological, renal, respiratory, genitourinary or major
             neurological (including stroke and chronic seizures) abnormalities or diseases.
             Participants with a history of uncomplicated kidney stones or childhood asthma may be
             enrolled in the trial at the discretion of the investigator.

          -  History of cancer (malignancy) - exceptions apply.

          -  History of significant multiple and/or severe allergies (e.g. food, drug, latex
             allergy), or has had an anaphylactic reaction or significant intolerability to
             prescription or non-prescription drugs or food.

          -  Positive for Human Immunodeficiency Virus (HIV).

          -  Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks
             prior to the pretrial (screening) visit.

          -  Participated in another investigational trial within 4 weeks prior to the pretrial
             (screening) visit.

          -  Nursing mother.

          -  Unable to refrain from or anticipates the use of any medication, including
             prescription and non-prescription drugs or herbal remedies beginning approximately 2
             weeks prior to the first dose of the 14 day methadone maintenance phase prior to Day
             1, throughout the trial, until the post-trial visit - exceptions apply.

          -  Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately
             equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits
             [29.5 mL/1 ounce]) per day - exceptions apply.

          -  Consumes excessive amounts of caffeine, 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.

          -  Has a positive screen for drugs with a high potential for abuse such as cocaine,
             amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines
             (exceptions apply), or opiates/opioids (apart from methadone as assigned maintenance
             therapy) on Day 1 that cannot be explained by concomitant medications, unless at the
             discretion of the principal investigator and the sponsor. Must have a negative Urine
             Drug Screen prior to randomization, with the exception of tetrahydrocannabinol (THC)
             and prescription benzodiazepines.

          -  Clinical Opiate Withdrawal Scale (COWS) score of >=5 prior to randomization.