A multicenter, placebo-controlled, double-blind, multiple-crossover study of Fentanyl Pectin Nasal Spray (FPNS) in the treatment of breakthrough cancer pain

Abstract

This randomized, double-blind, crossover study assessed the efficacy and tolerability of a new rapid onset nasal fentanyl formulation (Fentanyl Pectin Nasal Spray; FPNS) for breakthrough cancer pain (BTCP). Eighty-three of 114 patients experiencing one to four BTCP episodes/day while taking ≥60 mg/day of oral morphine or equivalent successfully identified an effective dose of FPNS during a titration phase and entered a double-blind phase in which 10 BTCP episodes were treated with this effective dose (7) or placebo (3). Compared with placebo, FPNS significantly improved mean summed pain intensity difference (SPID) from 10 min (P<0.05) until 60 min (P<0.0001), including the primary endpoint at 30 min (P<0.0001). FPNS significantly improved pain intensity (PI) scores as early as 5 min (P<0.05); pain intensity difference (PID) from 10 min (P<0.01); and pain relief (PR) scores from 10 min (P<0.001). More patients showed a clinically meaningful (≥ 2-point reduction in PI) pain reduction from 10 min onward (P ≤ 0.01) and 90.6% of the FPNS-treated versus 80.0% of placebo-treated BTCP episodes did not require rescue medication (P<0.001). Approximately 70% of patients were satisfied or very satisfied with the convenience and ease of use of FPNS. Only 5.3% of patients withdrew from treatment due to adverse events, no significant nasal effects were reported, and 87% of patients elected to continue open-label treatment post-study. In this short-term study, FPNS was safe, well tolerated, and rapidly efficacious for BTCP.

Long-term tolerability, efficacy and acceptability of fentanyl pectin nasal spray for breakthrough cancer pain

“…This is even more relevant when one considers that most patients reported moderate to severe pain at screening. Although efficacy was not studied in this long-term safety study, these findings are in line with the earlier studies that showed FPNS to be consistently effective compared with placebo [16] and IRMS [10].…”

“…This provides a more reproducible drug delivery with well-controlled peak concentrations and a concentration-time relationship that is consistent with the typical BTCP episode [21]. Two previous randomised, controlled phase III studies have demonstrated that FPNS provides superior pain relief compared with both placebo [16] and immediate-release morphine sulphate (IRMS) [10]. Both studies demonstrated that significant effects on pain could be recorded after 5 min following a dose, and significantly greater clinically meaningful reductions in pain intensity could be seen from 10 min after dosing.…”

Relationship between performance status and satisfaction with fentanyl pectin nasal spray

“…While a previous survey suggested that few patients had prior experience with a nasal route of analgesic medication (Walker et al, 2003), two recent randomized controlled studies of FPNS found that 69-80 % of patients were satisfied or very satisfied with the ease of use and convenience (Portenoy et al, 2010b;Davies et al, 2011b). It should be noted, however, that many of the patients in this "extension study" were pre-selected because of a successful response in the preceding double-blind trials.…”

Managing Breakthrough Pain

“…After a titration phase to determine the effective dose, the use of INFS at doses of 50 to 200 μg was associated with an onset of activity at 10 min and a more effective treatment of BTcP compared with placebo [24]. In a placebo-controlled, double-blind, crossover study, a pectin formulation of INFS was effective in the treatment of BTcP [25]. The only existing study comparing two different ROOs showed a decrease in pain intensity that was significantly greater with INFS than OTFC from 5 min post-dosing.…”