Long-Term Buprenorphine Implants for Treatment of Opioid Dependence: Safety Outcomes from Two Open-Label Extension Trials
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) 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 fifth 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. Modifications 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.