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 < 0.05) for SPID60 (mean [SD]: 7.7 [6.2] vs 4.6 [4.7]). The average onset of PR began at 5 minutes, with meaningful PR by <= 10 minutes. The proportion of episodes with >= 33% improvement in PI was 7% with FBT vs 3% with placebo at 5 minutes and with >= 50% was 17% vs 10% at 15 minutes. All periods showed similar results. Adverse events and patient discontinuations were generally typical of clinical opioid use. Conclusions. FBT showed continued clinically important analgesic effects and was generally well tolerated over 12 weeks of treatment.