Efficacy and Safety of the Seven-Day Buprenorphine Transdermal System in Opioid-Naive Patients with Moderate to Severe Chronic Low Back Pain: An Enriched, Randomized, Double-Blind, Placebo-Controlled Study

Context. This article presents the results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine. In this randomized, placebo-controlled study with an enriched enrollment design, the buprenorphine transdermal system (BTDS) was found to be efficacious and generally well tolerated. Objectives. This enriched, multicenter, randomized, double-blind study evaluated the efficacy, tolerability, and safety of BTDS in opioid-naive patients who had moderate to severe chronic low back pain. Methods. Patients who tolerated and responded to BTDS (10 or 20 mcg/hour) during an open-label run-in period were randomized to continue BTDS 10 or 20 mcg/hour or receive matching placebo. The primary outcome was "average pain over the last 24 hours" at the end of the 12-week double-blind phase, collected on an 11-point scale (0 = no pain, 10 = pain as bad as you can imagine). Sleep disturbance (Medical Outcomes Study subscale) and total number of supplemental analgesic tablets used were secondary efficacy variables. Results. Fifty-three percent of patients receiving open-label BTDS (541 of 1024) were randomized to receive BTDS (n = 257) or placebo (n 284). Patients receiving BTDS reported statistically significantly lower pain scores at Week 12 compared with placebo (least square mean treatment difference: -0.58, P = 0.010). Sensitivity analyses of the primary efficacy variable and results of the analysis of secondary efficacy variables supported the efficacy of BTDS relative to placebo. During the double-blind phase, the incidence of treatment-emergent adverse events was 55% for the BTDS treatment group and 52% for the placebo treatment group. Laboratory, vital sign, and electrocardiogram evaluations did not reveal unanticipated safety findings. Conclusion. BTDS was efficacious in the treatment of opioid-naive patients with moderate to severe chronic low back pain. Most treatment-emergent adverse events observed were consistent with those associated with the use of opioid agonists and transdermal patches. J Pain Symptom Manage 2011;42:903-917. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.