Dr Frank Gray

Indivior Ltd

Aims: To assess clinical efficacy/safety of RBP-6000 (long-acting, extended-release buprenorphine for monthly administration by subcutaneous injection) in phase III OUD trials.

Design: Study 1 (NCT02357901): double-blind, randomized, placebo-controlled, 24-week study. Study 2 (NCT02510014): open-label extension for Study 1 completers (roll-over) and <em>de novo subjects.

Setting: Non-residential studies conducted in the United States.

Participants: Treatment-seeking adults meeting DSM-5 criteria for moderate/severe OUD.

Interventions: Study 1: buprenorphine/naloxone induction, followed by RBP-6000 300/300mg (6x300mg), RBP-6000 300/100mg (2x300mg, then 4x100mg), or placebo (6x). Study 2: buprenorphine/naloxone induction, followed by RBP-6000 300 mg initially with flexible subsequent monthly doses (100 or 300 mg). All subjects received individualized counseling.

Measurements: Study 1 primary endpoint: cumulative distribution function for percentage abstinence (urine samples negative for opioids combined with self-reports negative for illicit opioid use [Weeks 5-24]; missing imputed as non-negative). Study 2 evaluated long-term safety/tolerability and efficacy.

Findings: Study 1 (n=504): both RBP-6000 treatment groups were significantly superior to placebo (P<0.0001) for primary efficacy endpoint (300/300mg, 41%; 300/100mg, 43%; placebo, 5% [mean values]). Among completers (n=245), mean percentage abstinence (Week 24) was 69% (300/300mg) and 60% (300/100mg). Study 2 (n=669): 61% of roll-over (n=174) and 76% of <em>de novo (n=206) completers were abstinent at Week 49. Safety data (Study 2): any TEAE (roll-over, 56%; <em>de novo 73%), serious TEAE (3%, 4%), severe TEAE (3%, 9%), TEAE leading to study discontinuation (2%, 3%). No unexpected safety signals were reported.

Conclusion: Efficacy was maintained with continued RBP-6000 dosing for up to 12 months ‘ treatment, with no new safety signals.

Co-Authors

Dr Barbara Haight Indivior Inc., Richmond, USA Dr Anne Andorn Indivior Inc., Richmond, USA Dr Celine M. Laffont Indivior Inc., Richmond, USA Dr Malcolm Young Indivior Inc., Richmond, USA Dr Aksana Jones Indivior Inc., Richmond, USA Dr Susan Learned Indivior Inc., Richmond, USA Dr Yue Zhao Indivior Inc., Richmond, USA Dr Frank Gray Indivior Inc., Richmond, USA Dr Christian Heidbreder Indivior Inc., Richmond, USA

Conflicts of interest:

All authors are employees of Indivior.