A Study to Evaluate Withdrawal Effects Following Dosing of Oxycodone/Naltrexone in Methadone-Maintained Subjects
Condition: Withdrawal Symptoms
MeSH terms: Substance Withdrawal Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      This single-center study is a randomized, double-blind, active-controlled, multiple-dose,
      parallel group study to evaluate the potential withdrawal effects, safety and tolerability,
      and pharmacokinetic and pharmacodynamic effects of multiple doses of oral intact
      Oxycodone/Naltrexone capsules compared to oxycodone in methadone-maintained opioid-dependent
      subjects. The study will consist of a Screening Phase, an inpatient Treatment Phase
      (including a methadone stabilization period, a placebo administration period, a treatment
      administration period and a safety/washout period), and a Follow-up Phase.
    

Detailed description: 
      Approximately 34 methadone-maintained opioid-dependent subjects will be enrolled in the
      study. All subjects will be admitted to the clinical study unit (CSU; Visit 2) for a 15-day
      (with 14 overnight stays) inpatient Treatment Phase visit. Subjects will first undergo a
      3-day methadone stabilization period (Days 1 to 3) in which all subjects' methadone
      administration time will be gradually shifted to the time of dosing that will be used
      throughout the Treatment Phase (approximately 8 am daily). Following the methadone
      dosing-time stabilization period, subjects will begin a 2-day oxycodone placebo
      administration period. On Day 4 and Day 5, all subjects will receive a total of 3 oxycodone
      placebo doses, separated by 6 hours each, starting from approximately one hour following
      methadone dose administration. Placebo will be administered in a single-blind manner.
      Starting on Day 6, subjects will be randomized in a 2:1 (Oxycodone/Naltrexone or Oxycodone)
      fashion to receive one of the following treatments in a double-blinded manner:

        -  Oxycodone/Naltrexone, multiple oral daily dosing for 5 days

        -  Oxycodone, multiple oral daily dosing for 5 days Subjects will receive one of the
           above-listed treatments three times daily, beginning approximately 1 hour following
           methadone dosing and every 6 hours until 3 doses have been administered. Subjects will
           be dosed in this manner for 5 consecutive days (Days 6 to 10). All subjects will remain
           confined in the CSU for 4 days after the first of three doses of study drug is
           administered on Day 10 for the safety/washout period, during which they will continue to
           be assessed and monitored for withdrawal effects. Subjects will be discharged
           approximately 96 hours after the first dose of study drug (oxycodone/naltrexone or
           oxycodone) administered on the morning of Day 10, if medically acceptable according to
           the investigator or designee. All subjects will receive daily phone calls until the
           Follow-up Phase during which subjects will be asked about the presence of withdrawal
           symptoms and any other adverse events (AEs).

      On Days 4 to 9, safety, withdrawal, pharmacokinetic and pharmacodynamic assessments will be
      performed up to 13 hours after the first of the three daily study drug doses is administered.
      Following Day 10 study drug administration, assessments will be completed until 96 hours
      after the first of the three daily study drug doses is administered on the morning of Day 10.

      The Follow-up Phase will be conducted approximately 10 to 14 days after the last drug
      administration on Day 10 or after early withdrawal from the study and will include standard
      safety assessments.
    

Intervention name(s): Oxycodone/Naltrexone Capsules; Oxycodone; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Oxycodone/Naltrexone to be taken with stable dose of Methadone; Oxycodone to be taken with stable dose of Methadone; 2 day placebo run in prior to test and active drug phase of study
Intervention MeSH terms: Naltrexone; Oxycodone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)