Safety and efficacy of Fentanyl Sublingual (SL) Spray in the treatment of breakthrough cancer pain

Background: This randomized, double-blind, placebo-controlled, phase 3 study evaluated the safety and efficacy of fentanyl sublingual (SL) spray for treatment of breakthrough cancer pain. Methods: Fentanyl SL spray doses of 100, 200, 400, 600, 800, 1200 (2x600), or 1600 (2x800) lg were available during the 21(+5)-day open-label titration and 21(+5)-day doubleblind study periods. The primary endpoint was summed pain intensity differences 30 minutes postdose (SPID30). All patients provided written informed consent; this study received approval from an Institutional Review Board. Results: Of 130 opioid-tolerant patients enrolled in the openlabel titration period, 98 (75%) were randomized to the double- blind period (mean age, 54.1 y). Median (range) dose of fentanyl SL spray in the double-blind period was 800 (100- 1600) μg. Mean (SD) SPID30 scores were 640.3 (458.8) for fentanyl SL spray and 399.6 (391.2) for placebo (difference, 240.7 [362.9]; P < 0.0001). Mean total pain relief at 30 minutes was significantly improved (P < 0.0001) in patients receiving fentanyl SL spray (78.3 [20.4]) versus placebo (61.0 [20.8]). The most frequently reported (≥ 5% of patients) adverse events during the titration period were nausea (13.1%), somnolence (8.5%), dizziness (7.7%), vomiting (7.7%), pyrexia (6.2%), diarrhea (5.4%), and peripheral edema (5.4%). In the double-blind period, the most frequently reported adverse events were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Three deaths were reported; none was considered related to study drug. Conclusions: Fentanyl SL Spray was significantly more effective at relieving breakthrough cancer pain compared with placebo. No new safety concerns were identified.