Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects
Condition: Opioid Related Disorder
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open-label study in treatment seeking opioid-dependent subjects for safety,
      tolerability, pharmacokinetics (PK), efficacy markers, and opioid receptor availability of
      subcutaneous injections of depot buprenorphine after induction and stabilization of treatment
      seeking subjects onto Subutex.

      Subjects were planned to receive 4 subcutaneous (SC) injections of RBP-6000 separated by 28
      days (Cohorts 1-5) or 6 SC injections of RBP-6000 separated by 28 days (Cohort 6) after a
      13-day induction and dose stabilisation period on SUBUTEX Sublingual (SL) tablet at dose
      levels of 8-24 mg.
    

Detailed description: 
      -  Open-label SUBUTEX Sublingual Tablet Induction and Stabilisation Period After completing
           the screening period, subjects entered an open-label SUBUTEX SL tablet induction and
           stabilisation period to achieve stable daily doses of 8 mg, 12 mg, 14 mg, 24 mg or 8 -
           24 mg (variable) during a 13 day inpatient (Day -14 to Day -1) period.

        -  Open-label Treatment Phase On Day 1, eligible subjects discontinued use of SUBUTEX SL
           tablet and received a subcutaneous (SC) injection of RBP-6000. The dose of RBP-6000
           received and the cohort to which a subject was assigned depended upon the SUBUTEX SL
           tablet dose on Day -1.

             -  Injection 1 (Day 1): 3 days inpatient post-dose (Day 1 to Day 3) and outpatient
                visits (Day 4 to Day 28); serial pharmacokinetic (PK) samples

             -  Injection 2 (Day 29): 60-hour inpatient pre-dose and post-dose (Day 28 to Day 31)
                and outpatient visits (Day 32 to Day 56); sparse PK samples

             -  Injection 3 (Day 57): 60-hour inpatient pre-dose and post-dose (Day 56 to Day 59)
                and outpatient visits (Day 60 to Day 84); sparse PK samples

             -  Injection 4 (Day 85): 60-hour inpatient pre-dose and post-dose (Day 84 to Day 87)
                and outpatient visits (Day 88 to Day 113 [or Day 112 for Cohort 6]); serial PK
                samples

             -  Cohort 6 ONLY: Injection 5 (Day 113): 60-hour inpatient pre-dose and post-dose (Day
                112 to Day 115) and outpatient visits (Day 116 to Day 140); serial PK samples

             -  Cohort 6 ONLY: Injection 6 (Day 141): 60-hour inpatient pre- and post-dose (Day 140
                to Day 143) and outpatient visits (Day 144 to Day 169); serial PK samples

             -  Safety Follow-up: weekly visits up to 60 days post-Injection 4 (PK Day 114 to Day
                141) for subjects in Cohorts 1-5 who did not take part in the positron emission
                tomography (PET) imaging sub-study and up to 60 days post-Injection 6 (PK Day 169
                to Day 197) for subjects in Cohort 6

      The objective of the PET imaging sub-study was to evaluate the relationship between
      buprenorphine plasma levels and the ability of the 200 mg and 300 mg doses of RBP-6000 to
      reduce mu-opioid receptor availability measured with [11C]carfentanil and positron emission
      tomography (PET) scans. This objective was exploratory in nature and results are not reported
      as part of these summary results.
    

Intervention name(s): RBP-6000; Subutex
Intervention type(s): Drug; Drug
Intervention description(s): 18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and given on alternate sides of the participant's abdomen.; Participants were inducted and stabilized over a 14-day period (study days -14 to -1) on SUBUTEX sublingual tablets. Tablets are placed under the tongue until dissolved.
Other intervention name(s): buprenorphine; buprenorphine
Intervention MeSH terms: Buprenorphine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Opioid Dependence, Buprenorphine, Depot, SUBUTEX, RBP-6000