Weekly and monthly subcutaneous buprenorphine depot formulations vs daily sublingual buprenorphine with naloxone for treatment of opioid use disorder a randomized clinical trial

Michelle R. Lofwall, Sharon L. Walsh, Edward V. Nunes, Genie L. Bailey, Stacey C. Sigmon, Kyle M. Kampman, Michael Frost, Fredrik Tiberg, Margareta Linden, Behshad Sheldon, Sonia Oosman, Stefan Peterson, Michael Chen, Sonnie Kim

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127 Scopus citations

Abstract

IMPORTANCE: Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations. OBJECTIVE: To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder. DESIGN, SETTING, AND PARTICIPANTS: This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder. INTERVENTIONS: Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group). MAIN OUTCOMES AND MEASURES: Primary end points tested for noninferioritywere response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority. RESULTS: A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0%difference (95%CI, -4.0%to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7%difference (95%CI, -0.1%to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group. CONCLUSIONS AND RELEVANCE: Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages.

Original languageEnglish
Pages (from-to)764-773
Number of pages10
JournalJAMA Internal Medicine
Volume178
Issue number6
DOIs
StatePublished - Jun 2018

Bibliographical note

Funding Information:
reported receiving research funding from Braeburn Pharmaceuticals, Inc, and consulting fees from Braeburn Pharmaceuticals, Inc, and Indivior. Dr Walsh reported receiving contract research funding and consulting fees from Braeburn Pharmaceuticals, Inc, consulting fees from Camurus AB, and travel support from Indivior. Dr Nunes reported receiving contract research funding from Braeburn Pharmaceuticals, Inc, Alkermes, Inc, and Brainsway, Inc, and unpaid consulting for Alkermes, Inc. Dr Bailey reported receiving research funding, advisory board, and traveling support from Braeburn Pharmaceuticals, Inc; advisory board, speaker bureau fees, and travel support from BioDelivery Science International, Inc, and Alkermes, Inc; and research funding and speaker fees from Indivior. Dr Kampman reported receiving research funding from Braeburn Pharmaceuticals, Inc, Indivior, and Opiant Pharmaceuticals, Inc. Dr Frost reported receiving research funding and consulting fees from Braeburn Pharmaceuticals, Inc; honorarium for talks from Indivior; and consulting fees and speaking honorarium from BioDelivery Sciences International, Inc. Drs Tiberg and Linden reported being employees of Camurus AB. Mss Sheldon and Oosman and Dr Kim reported being employees of Braeburn Pharmaceuticals, Inc. Dr Chen reported receiving consulting fees from Braeburn Pharmaceuticals, Inc. Dr Peterson reported receiving consulting fees from Camurus AB and AstraZeneca Ltd. No other disclosures were reported.

Funding Information:
Funding/Support: The study was supported by Braeburn Pharmaceuticals, Inc, and by grant UL1TR001998 from the University of Kentucky Center for Clinical and Translational Science for research services and facilities for the study at this site.

Publisher Copyright:
© 2018 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • Internal Medicine

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