Low-Dose Transdermal Buprenorphine for Low Back Pain An Enriched Enrollment Randomized Withdrawal Placebo-Controlled Study

摘要

Objectives : The aim of this study was to compare the efficacy and safety profile of the buprenorphine transdermal system (BTDS) with placebo in patients with moderate to severe low back pain. Methods : In this enrich enrollment randomized withdrawal design study, the subjects who demonstrated analgesic benefit from and tolerability to BTDS treatment in an open-label run-in phase were randomized to receive either BTDS or a matching placebo during a 12-week double-blind phase. The primary efficacy variable was defined as the time to inadequate pain relief. Results : Time to inadequate pain relief was significantly longer for the BTDS group versus the placebo group (P = 0.0025). Kaplan-Maier estimates of time-to-event showed that the proportion of subjects who experienced inadequate pain relief in the placebo group reach 25% by Day 9 ; while the proportion of subjects in the BTDS group did not reach 25% by Day 85 (the end of the double-blind phase), though the median survival times were not estimated for either group. The proportion of subjects with inadequate pain relief during the double-blind phase, one of the secondary efficacy variables, was significantly lower in the BTDS group compared with the placebo group (Placebo : 44.9%, BTDS : 21.7%, P = 0.0064). The most common adverse events which occurred during BTDS exposure in this study were opioid-related adverse events (nausea/ vomiting) and application site reactions. Conclusion : BTDS was effective in the treatment of subjects with moderate to severe low back pain. Adverse events observed in this study were generally well tolerated.