Buprenorphine transdermal delivery system in adults with persistent noncancer-related pain syndromes who require opioid therapy: a multicenter, 5-week run-in and randomized, double-blind maintenance-of-analgesia study.

OBJECTIVE: This study compared the efficacy and safety profile of buprenorphine transdermal delivery system (BTDS) and placebo in subjects with persistent noncancer-related pain who required opioid analgesics.

METHODS: This was a multicenter, double-blind, parallel-group study in adult subjects (age >/=18 years) with at least a 2-month history of noncancer-related pain for which they received oral opioid combination agents. The study employed a maintenance-of-analgesia, or randomized-withdrawal, design. During a 7- to 21-day open-label run-in phase, all subjects received BTDS, titrated as needed. Subjects who achieved stable pain control and were able to tolerate BTDS in the run-in phase were randomly assigned to continue BTDS at the dose achieved during the run-in phase or to receive placebo for up to 14 days. Acetaminophen 500-mg tablets were provided as escape (rescue) medication. Subjects completed the study on day 14 or when they met predefined criteria for ineffective treatment: requiring >1 g of acetaminophen as escape medication on any day of the double-blind evaluation phase, requiring a change in study drug dose, having difficulty keeping the patch affixed, or discontinuing because of ineffective treatment without meeting any of the first 3 criteria. The primary efficacy variable was the proportion of subjects with ineffective treatment. Secondary efficacy variables were the time to ineffective treatment; the proportion of subjects who reached ineffective treatment or discontinued for any reason other than ineffective treatment; and the amount of escape medication used. Assessment of the safety profile was based on adverse events and changes in vital signs and physical and laboratory findings.

RESULTS: Five hundred eighty-eight subjects entered the open-label run-in phase, and 267 (129 BTDS, 138 placebo) were subsequently randomized to doubleblind treatment. Demographic characteristics were similar between the double-blind BTDS and placebo groups (61.2% and 63.8% female, respectively; 99.2% and 98.6% white; mean [SD] age, 56.2 [13.3] and 59.2 [11.5] years). In the primary efficacy analysis, the proportion of subjects with ineffective treatment was lower with BTDS than with placebo (51.2% vs 65.0%; 95% CI, 1.09-2.95); the odds of ineffective treatment were 1.79 times greater for placebo relative to BTDS (P = 0.022). In the secondary efficacy analyses, the median time from the first dose of double-blind study drug to ineffective treatment was significantly longer with BTDS than with placebo (median, 10 vs 3 days; P = 0.011). The proportion of subjects who reached ineffective treatment or discontinued for reasons other than ineffective treatment was lower in the BTDS group compared with the placebo group (55.0% vs 67.9%); the odds of ineffective treatment or discontinuation for a reason other than ineffective treatment was 1.76 times greater with placebo compared with BTDS (P = 0.028). The mean amount of escape medication used was significantly lower in the BTDS group than in the placebo group (1.7 vs 2.2 acetaminophen tablets per day; P = 0.015). The most common adverse events in the open-label run-in or double-blind phase occurring at a higher incidence with BTDS than with placebo were pruritus at the patch application site (9.3% vs 5.1%, respectively), headache (3.9% vs 2.2%), and somnolence (2.3% vs 0.7%).

CONCLUSION: In this population of adult subjects with persistent noncancer-related pain who required opioid therapy, BTDS use was associated with analgesic efficacy and was generally well tolerated. Results of this study were presented in part at the annual meeting of the American Pain Society, March 30-April 2, 2005, Boston, Massachusetts.