Effective dose titration of fentanyl sublingual spray in patients with breakthrough cancer pain: results from the open-label phase of a double-blind, placebo-controlled study

Abstract

Breakthrough cancer pain (BTCP) is commonly managed with formulations of transmucosal fentanyl. A novel sublingual formulation of fentanyl, fentanyl sublingual spray, has been developed to enhance the rate and extent of fentanyl absorption and potentially the onset of analgesia. This analysis presents results from the 26-day open-label titration phase of a phase 3, randomized, double-blind, placebo-controlled study. Opioid-tolerant patients with 1-4 episodes of BTCP/d were enrolled. For randomization into double-blind treatment, patients must have successfully titrated to a dose (100-1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. The Treatment Satisfaction Questionnaire for Medication was assessed at screening to determine satisfaction with previous BTCP medication and at the end of titration to determine satisfaction with fentanyl sublingual spray. Of 130 patients undergoing titration, 98 (75%) achieved a successful dose; the median dose was 800 mcg, and the most common doses were 800 mcg (22.4%) and 1200 mcg (20.4%). Of 32 (25%) patients that withdrew from titration, only 3 (2.3%) were unable to establish an effective dose. At the end of titration, 89% were satisfied, very satisfied, or extremely satisfied with fentanyl sublingual spray, compared with 41% with their previous BTCP medication. Notably, 90% were at least satisfied with the onset of effect of fentanyl sublingual spray versus 21% in relation to previous BTCP treatment. Seventy-eight patients (60%) reported ≥1 adverse event (AE). Thirty-three AEs (25.4%) were considered probably related to treatment, the most common being nausea (6.2%) and somnolence (4.6%). These data demonstrate that in patients with BTCP, fentanyl sublingual spray can be safely titrated to an effective dose, and many prefer this treatment over previous BTCP medications. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.