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Original Investigation
September 2017

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use DisorderA Randomized Clinical Trial

Author Affiliations
  • 1Center on Drug and Alcohol Research, University of Kentucky, Lexington
  • 2Department of Psychiatry, Columbia University, New York, New York
  • 3Vince and Associates Clinical Research, Overland Park, Kansas
  • 4Altreos Partners, Toronto, Ontario, Canada
  • 5Camurus, Lund, Sweden
  • 6Braeburn Pharmaceuticals, Princeton, New Jersey
JAMA Psychiatry. 2017;74(9):894-902. doi:10.1001/jamapsychiatry.2017.1874
Key Points

Question  Can a novel sustained release buprenorphine weekly injectable formulation (CAM2038) produce robust opioid blockade and opioid withdrawal suppression?

Findings  This randomized clinical trial enrolled individuals with opioid use disorder but not seeking treatment and examined the response to hydromorphone before and after administration of CAM2038 at 2 doses. Both CAM2038 doses produced robust opioid blockade on the primary outcome measure of subjective response for liking of hydromorphone and immediate and sustained withdrawal suppression.

Meaning  Weekly injectable CAM2038 shows promise as a potential treatment for individuals with opioid use disorder.

Abstract

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 18 mg 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 24 mg (n = 22) or 32 mg (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 point was 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 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P < .001, and CAM2038, 32 mg: effect size, 0.753; P < .001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P < .001, and CAM2038, 32 mg: 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 24 mg; trough concentration = 0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32 mg).

Conclusions and Relevance  CAM2038 weekly, 24 and 32 mg, 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.

Trial Registration  Clinicaltrials.gov Identifier: NCT02611752

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