Importance: Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation. Objective: To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD. Design, Setting, and Participants: This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit). Interventions: A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24mg (n = 22) or 32mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13). Main Outcomes and Measures: The primary end pointwas maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes. Results: A total of 46 of 47 randomized participants (mean [SD] age, 35.5  years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24mg: effect size, 0.813; P < .001, and CAM2038, 32mg: effect size, 0.753; P < .001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24mg: effect size, 0.617; P < .001, and CAM2038, 32mg: effect size, 0.751; P < .001). CAM2038 produces a rapid initial rise of buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration = 0.822 and 1.23 ng/mL for weeks 1 and 2, respectively, with 24mg; trough concentration = 0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32mg). Conclusions and Relevance: CAM2038 weekly, 24 and 32mg, was safely tolerated and produced immediate and sustained opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with the further benefit of obviating the risk for misuse and diversion of daily buprenorphine while retaining its therapeutic benefits.
|Number of pages||9|
|State||Published - Sep 2017|
Bibliographical noteFunding Information:
Sheldon are employees of the sponsor, Braeburn Pharmaceuticals. Dr Tiberg is an employee of Camurus, a partner to the sponsor. Drs Walsh, Comer, Lofwall, and Vince received research contract support from Braeburn Pharmaceuticals to complete the study. Drs Walsh, Lofwall, and Levy-Cooperman and Mr Nuzzo received consultant fees from Braeburn Pharmaceuticals, and Drs Walsh and Comer received consulting fees from Camurus. Dr Comer has received compensation (in the form of partial salary support) from investigator-initiated studies supported by Endo Pharmaceuticals and Indivior PLC/Reckitt-Benckiser Pharmaceuticals. No other disclosures were reported.
© 2017 American Medical Association. All rights reserved.
ASJC Scopus subject areas
- Psychiatry and Mental health