Transition of Patients with Opioid Use Disorder from Buprenorphine to Extended-Release Naltrexone: A Randomized Clinical Trial Assessing Two Transition Regimens.

ABSTRACT

BACKGROUND AND OBJECTIVE: When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study. METHODS: In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (11) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX. RESULTS: There was no statistical difference between groups for participants receiving a first dose of XR-NTX 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Low ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;0000-00).