Multiple Dose Study of Blockade of Opioid Effects by Injections of Buprenorphine in Participants With Opioid Disorder
Condition: Opioid Use Disorder
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a multiple-dose study in non-treatment seeking male and female subjects with moderate
      to severe opioid use disorder who meet criteria from the Diagnostic and Statistical Manual of
      Mental Disorders, 5th Edition (DSM-5) to evaluate the effectiveness of RBP-6000 to block the
      effects of exogenous opioids.

      The primary objective of this study was to demonstrate that the "Drug Liking" visual analog
      scale (VAS) measured after challenge with 6 mg (Dose 1) and 18 mg (Dose 2) hydromorphone was
      noninferior to the "Drug Liking" visual analog scale (VAS) measured after challenge with
      placebo at Weeks 1-4 post first injection of subcutaneous buprenorphine 300 mg (RBP-6000).
    

Detailed description: 
      For the hydromorphone challenge testing, subjects were randomized and assigned to 1 of 6
      sequences during each week of hydromorphone challenge sessions.

      On Day -18, subjects who met initial eligibility criteria were admitted to the clinical
      facility for the baseline hydromorphone challenge. If the subject had acceptable
      hydromorphone responses to the hydromorphone challenge, they remained confined to the
      clinical facility for induction on SUBOXONE sublingual film. Once it was confirmed that a
      subject was experiencing opioid withdrawal, as evidenced by a Clinical Opiate Withdrawal
      Scale (COWS) score greater than 12, the subject was inducted on SUBOXONE sublingual film.
      Multiple doses were allowed while subjects were reaching a stable dose until Day -9 when
      subjects were stabilized on a dose of SUBOXONE 8 mg - 24 mg. SUBOXONE sublingual film was
      administered daily at approximately the same time of day (± 1 hour) once the dose was
      stabilised. There was a hydromorphone challenge conducted on days -3 to -1. The last day of
      SUBOXONE dosing was day -1.

      On Day 1, participants who met all inclusion/exclusion criteria and dosing criteria stopped
      receiving SUBOXONE sublingual film and received Injection 1 of RBP-6000 containing 300 mg
      buprenorphine. Participants returned in the evening of Days 4, 11, 18, and 25 to begin
      inpatient stays of 3 consecutive days (starting with Days 4-7 [and equivalent for subsequent
      weeks]). During these inpatient visits, subjects underwent randomised hydromorphone
      challenges, PK sample collection, Reinforcing Effects Tasks, and safety assessments.

      On Day 29, participants received the second injection of RBP-6000 containing 300 mg
      buprenorphine (Injection 2). Participants returned in the evening on Days 32, 39, 46, 53, 60,
      67, 74, and 81 to begin inpatient states of 3 consecutive days (starting with days 32-35 [and
      equivalent for subsequent weeks]). During these inpatient visits, subjects underwent
      randomised hydromorphone challenges, pharmacokinetic (PK) samples collection, Reinforcing
      Effects Tasks, and safety assessments. A window of ± 1 day was allowed for all visits, except
      the Day 53-56 visit, which was required by the protocol to be completed on those days.
    

Intervention name(s): Buprenorphine; buprenorphine and naloxone; hydromorphone; placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): A subcutaneous depot injection of buprenorphine 300 mg was delivered using the ATRIGEL® Delivery System on study days 1 and 29. As the depot degrades, buprenorphine is released into systemic circulation over an extended period of time.; Buprenorphine and naloxone (SUBOXONE® sublingual film) is given to participants on days -14 to day -1 (the SUBOXONE sublingual film stabilization period) or as soon as they start to experience withdrawal symptoms. SUBOXONE sublingual film may be initially administered several times daily until a stable dose between 8 mg and 24 mg daily is established.; Hydromorphone IM challenges are administered during the screening period (days -17 to -15), on days -3 to -1 during the buprenorphine and naloxone (SUBOXONE sublingual film) stabilization period, and weekly during the 12-week treatment period after administration of RBP-6000. Each challenge consists of 3 days during which participants are randomly administered 0 mg (placebo), 6 mg and 18 mg hydromorphone via intramuscular (IM) injection daily in varying blinded sequences.
Additionally, hydromorphone can also be earned during the afternoon Reinforcing effects tasks sessions up to the same randomized dose received in the hydromorphone challenge that morning (or money can be chosen).; Placebo for hydromorphone administered via intramuscular injection during each challenge.
Other intervention name(s): RBP-6000; Subcutaneous buprenorphine; SUBOXONE® sublingual film; dihydromorphinone; 0.45% normal saline
Intervention MeSH terms: Buprenorphine; Hydromorphone; Naloxone
Intervention model: Single Group Assignment
Intervention model description: All subjects were dispensed the same 300 mg dose of the investigational drug, RBP-6000. They were all also exposed to 0 mg, 6 mg, and 18 mg of hydromorphone for challenges sequentially in a randomized manner.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Opioid dependent; Buprenorphine; Suboxone Film; Opioid blockade; Hydromorphone challenge