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
Intervention: Buprenorphine; buprenorphine and naloxone; hydromorphone; placebo
Intervention description: 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.
Intervention MeSH terms: Buprenorphine; Hydromorphone; Naloxone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Masking description: The investigational drug, RBP-6000, was administered unblinded. The hydromorphone challenges used to measure the effectiveness of RBP-6000 were known and randomized in blinded fashion only to determine the order in which they were administered, with participant and clinical staff blinded to the order of dosing.
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Opioid dependent; Buprenorphine; Suboxone Film; Opioid blockade; Hydromorphone challenge

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
             criteria for moderate or severe opioid use disorder at screening and are not seeking
             opioid use disorder treatment

          -  Body mass index of >= 18.0 to <= 33.0 kg/m^2

          -  Females - women of childbearing potential (defined as all women who are not surgically
             sterile or postmenopausal for at least 1 year prior to informed consent) must have
             negative pregnancy test prior to enrollment and must agree to use a medically
             acceptable means of contraception from screening through at least 3 months after the
             last dose of study drug

          -  Male subjects with female partners of child-bearing potential must agree to use
             medically acceptable contraception from screening through at least 3 months after the
             last dose of study drug

        Exclusion Criteria:

          -  Subjects with any current diagnosis requiring chronic opioid treatment

          -  Subjects who currently meet the criteria for diagnosis of moderate or severe substance
             use disorder by DSM-5 criteria for any substances other than opioids, caffeine, or
             nicotine.

          -  Subjects who have abused or used buprenorphine within 14 days prior to informed
             consent.

        Other protocol-defined criteria may apply.