Efficacy and Safety of Fentanyl Inhalant for the Treatment of Breakthrough Cancer Pain: A Multicenter, Randomized, Double- blind, Placebo-controlled Trial

Abstract BackgroundBreakthrough cancer pain (BTcP) has a negative impact on patients’ quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. Methods Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 minutes (SPID30). Results A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p<0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 minutes and maintained for up to 60 minutes. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 minutes, PR30 (pain relief scores at 30 minutes) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. Conclusion Fentanyl inhalant was efficacious, safe, and well tolerated in the management of BTcP. Trial registration ClinicalTrials.gov: NCT05531422