ABSTRACT
PURPOSE: The aims of this study were to explore the efficacy of intranasal fentanyl spray* (INFS) 400 µg to evaluate 12-week tolerability of the nasal mucosa and to explore safety data for all dose strengths of INFS in patients with cancer-related breakthrough pain (BTP). METHODS: Patients received a test dose of INFS 50 µg, followed by a titration phase. Those patients with doses titrated to 200 or 400 µg entered a randomized, double-blind, cross-over efficacy phase, in which 8 episodes of BTP were randomly treated with INFS 400 µg (6 episodes) and placebo (2 episodes), followed by a tolerability phase. Patients with doses titrated to 50 or 100 µg entered the tolerability phase directly. Primary outcome was measured by pain intensity difference at 10 minutes, analyzed using ANCOVA, and presented as least square mean difference. Examination of the nasal cavity was conducted at inclusion and after 12 weeks of treatment by an otorhinolaryngologist. FINDINGS: Forty-six patients were included. Thirty-eight patients' doses were titrated to an effective dose of INFS; 50 µg (n = 8), 100 µg (n = 9), 200 µg (n = 9), and 400 µg (n = 12); 15 patients entered the efficacy phase and 31 entered the tolerability phase. In the efficacy phase, 88 and 29 episodes of BTP were treated with INFS 400 µg and placebo, respectively. Pain intensity difference at 10 minutes least square mean for INFS 400 µg was 2.5 (95% CI, 1.42-3.49) (P < 0.001) and least square mean difference between INFS 400 µg and placebo was 1.1 (95% CI, 0.41-1.79) (P = 0.002). Runny nose (10%) and change in color of the mucosa (9%) were the most frequent findings of nasal examination, and nausea and dizziness were the most frequent treatment-related adverse events. One serious adverse event (ie, respiratory depression) was considered related to INFS. IMPLICATIONS: INFS 400 µg is effective and nasal tolerability and overall safety profile is acceptable during 12 weeks of use. ClinicalTrials.gov identifier: NCT01429051.
