a SciTechnol journal Research Article Dammerman et al., J Addict Behav Ther Rehabil 2017, 6:1 DOI: 10.4172/2324-9005.1000162 Journal of Addictive Behaviors, Therapy & Rehabilitation All articles published in Journal of Addictive Behaviors, Therapy & Rehabilitation are the property of SciTechnol, and is protected by copyright laws. Copyright © 2017, SciTechnol, All Rights Reserved. International Publisher of Science, Technology and Medicine Long-Term Buprenorphine Implants for Treatment of Opioid Dependence: Safety Outcomes from Two Open-Label Extension Trials Dammerman R 1 *, Bailey GL 2 , Beebe KL 3 , Chen M 4 , Rosenthal RN 5 , Sigmon SC 6 and Ling W 7 Abstract Objective: To assess long-term exposure to buprenorphine implants (BIs) for opioid dependence in two open-label extension clinical trials. Methods: Two six-month, open-label, multicenter extension studies of BI (Clinicaltrials.gov NCT01262261, NCT00630201) were conducted with opioid-dependent adult participants who had completed 24 weeks of BI treatment in prior phase 3 trials. Subjects received four subdermal implants, each containing 80 mg buprenorphine hydrochloride. Supplemental sublingual buprenorphine or insertion of a ffth implant were available for patients meeting criteria for opioid craving or withdrawal at investigator discretion. Safety of BI was evaluated using adverse events (AEs), abnormalities in physical exams, and vital signs. Additional outcomes included plasma concentrations of buprenorphine, ratings of opioid withdrawal symptoms, and craving and treatment retention. Results: A total of 62/88 and 85/163 eligible participants continued in Study 1 and Study 2, respectively. Patient retention rates were 74.2% (46/62) and 78.8% (67/85) in Study 1 and 2, respectively. In Study 1, 47/62 participants (75.8%) experienced 329 treatment- emergent AEs; in Study 2, 57/85 participants (67.1%) experienced 172 AEs. Modifcations to the implantation procedure between Study 1 and Study 2 resulted in a numerical decrease in AEs. Of these AEs, 103/329 (31.3%) in Study 1 were implant site- related; 19/57 (11.0%) in Study 2 were implant site-related. Mean concentrations of buprenorphine were stable from weeks 4 to 24, and cravings and withdrawal were well controlled. Conclusion: The use of BI up to one year appears safe. Modifcations in the surgical technique resulted in a reduction in the overall number of AEs. Keywords *Corresponding author: Ryan Dammerman, MD, PhD, Senior Director, Medical Affairs, Braeburn Pharmaceuticals, 47 Hulfsh Street, Suite 441, Princeton, NJ 08542, USA, Tel: (412) 983-5973; E-mail: ryan@braeburnpharma.com Received: January 20, 2017 Accepted: March 20, 2017 Published: March 27, 2017 Introduction Opioid abuse and dependence have reached epidemic proportions in the United States, resulting in premature death, criminal activity, and other serious consequences that cost almost $56 billion annually [1-6]. In 2014, nearly 50,000 people in the United States died from drug overdoses, more than any previous year on record [7]. Since 2000, rates of death involving opioid overdoses have increased by 200% [7]. Recent increases in opioid- related overdoses are particularly concerning, with three- and six- fold increases in overdose deaths related to prescription opioids and heroin, respectively, between 2001 and 2014 [8]. Extended maintenance with sublingual buprenorphine (SL BPN) is an eficacious treatment for opioid addiction [9-13]. However, the widespread adoption of buprenorphine by treatment providers may be limited by concerns regarding patient nonadherence, abuse, or accidental pediatric exposure to the medication [14-17]. Indeed, recent reports have noted some degree of buprenorphine nonadherence among patients, which could erode the clinical benefits being produced by the expansion of buprenorphine into general medical settings [16,18]. Even under supervision, between 15% and 30% of participants reported removing or diverting an oral buprenorphine dose over a six-month period [19]. A novel, sustained-release formulation of buprenorphine, delivered via subdermal implants, was designed to provide sustained plasma concentrations of buprenorphine for up to six months, which may eliminate the need for daily dosing and reduce need for take- home doses. Previous phase 3, double-blind, placebo-controlled trials were conducted with opioid-dependent subjects treated for six months with urine toxicology testing conducted thrice weekly [20,21]. In these studies, buprenorphine implants (BI) were superior to placebo on outcomes of illicit opioid abstinence, retention in treatment, and ratings of opioid withdrawal and cravings. Further, BI was superior to SL BPN for control of withdrawal and cravings. Te purpose of this study was to evaluate long-term exposure to BIs for opioid dependence in two open-label extension clinical trials in which subjects who had previously completed 24 weeks of BI treatment subsequently received BI for an additional 24 weeks. Te present study represents the longest duration exposure evaluated to date with this novel, sustained-release formulation of buprenorphine. Materials and Methods Study design Two six-month, open-label, multicenter clinical trials of BI were conducted with adult participants with a history of opioid dependence who had completed 24 weeks of treatment in prior phase 3 trials evaluating BI [20,21]. In Study 1, all participants had previously received active or placebo implants. In Study 2, participants had previously received active implants, placebo implants, or SL BPN. Both trials were conducted in compliance with regulations and guidelines governing Good Clinical Practice and in accordance with the Declaration of Helsinki, with all participants providing written consent prior to participation. Participants Participants aged 18 to 65 years were eligible for inclusion if they had successfully completed 24 weeks of prior study treatment and volunteered to continue. Participants in the core blinded studies