A Novel 12-Week Study, with Three Randomized, Double-Blind Placebo-Controlled Periods to Evaluate Fentanyl Buccal Tablets for the Relief of Breakthrough Pain in Opioid-Tolerant Patients with Noncancer-Related Chronic Pain

Objective. To evaluate the time of onset, overall efficacy, and safety of fentanyl buccal tablet (FBT) for noncancer-related breakthrough pain (BTP) in opioid-tolerant adults over 12 weeks. Design. A novel 12-week study that mimicked clinical practice with dose titration to effective dose, open-label treatment, and three randomized, double-blind, placebo-controlled, multiple-crossover periods at weeks 4, 8, and 12. For each double-blind period, study patients received nine doses (FBT = 6, placebo = 3) in a randomized sequence. Setting. Twenty-one study centers in the United States. Population. Opioid-tolerant adults with noncancer-related chronic pain and BTP. Outcome Measures. The primary outcome was the sum of the pain intensity differences (PID) 5–60 minutes post dose (SPID60) during the final double-blind period. Secondary outcomes included pain relief (PR), meaningful PR, and proportion of episodes with a PID of ≥33% and ≥50%. Results. Of 148 patients who entered the titration phase, 105 (71%) achieved a successful dose and 81 (55%) participated in all three assessment periods in the study. The final RCT assessment period results demonstrated continued efficacy of FBT vs placebo (P