title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Purdue Pharma L.P., Stamford, Connecticut 06901-3431, USA. Deborah.Steiner@pharma.com
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Steiner
authors.forename: Steve
authors.initials: S
authors.lastname: Sitar
authors.forename: Warren
authors.initials: W
authors.lastname: Wen
authors.forename: Gosford
authors.initials: G
authors.lastname: Sawyerr
authors.forename: Catherine
authors.initials: C
authors.lastname: Munera
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ripa
authors.forename: Craig
authors.initials: C
authors.lastname: Landau
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine