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

• Published in: Journal of pain and symptom management Vol. 42; no. 6; pp. 903 - 917
• Main Authors: Steiner, Deborah J., Sitar, Steve, Wen, Warren, Sawyerr, Gosford, Munera, Catherine, Ripa, Steven R., Landau, Craig
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2011; Elsevier
• Subjects: Administration, Cutaneous; Adult; Aged; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Anesthesia & Perioperative Care; Biological and medical sciences; Buprenorphine; Buprenorphine - administration & dosage; Buprenorphine - adverse effects; Buprenorphine - therapeutic use; Chronic low back pain; Chronic pain; Diseases of the osteoarticular system; Diseases of the spine; Double-Blind Method; Efficacy; Electrocardiography; enrichment; Female; Humans; Low Back Pain - drug therapy; Male; Medical sciences; Middle Aged; Opioids; Pain Measurement; Pain Medicine; Pharmacology. Drug treatments; randomized controlled trials; Safety; transdermal; Treatment Outcome; chronic low back pain; enrichment; Buprenorphine; randomized controlled trials; transdermal; Enrichment; Lumbar spine; Toxicity; Low back pain; Diseases of the osteoarticular system; Opiates; Spine disease; Narcotic analgesic; Opioid peptide; Percutaneous route; Randomization; Pain; Rachialgia; Safety; Delivery system; Human; Transdermal system; Treatment efficiency; Randomized controlled trial; Chronic; Placebo; Dosage form; Double blind study
• ISSN: 0885-3924; 1873-6513; 1873-6513
• DOI: 10.1016/j.jpainsymman.2011.04.006

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. This enriched, multicenter, randomized, double-blind study evaluated the efficacy, tolerability, and safety of BTDS in opioid-naïve patients who had moderate to severe chronic low back pain. 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. 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. BTDS was efficacious in the treatment of opioid-naïve 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.