Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.

ABSTRACT

BACKGROUND: The effectiveness of fluticasone propionate (FP) aqueous nasal spray in the treatment of rhinitis has been demonstrated in multiple controlled clinical studies. The onset of therapeutic effect of FP in these clinical trials appears to occur within 12 hours after administration of the initial dose. OBJECTIVE: This article presents an analysis from previous clinical trials that examined the efficacy of intranasal FP in patients with rhinitis to ascertain whether the time to onset of the therapeutic effect of this medication could be determined. METHODS: Completed randomized, double-blind, placebo-controlled studies with FP were evaluated to determine whether onset of effect could be evaluated based on the study designs. A study was deemed acceptable for evaluation of onset of effect if at least one evaluation of the intensity of nasal symptoms was completed within 12 hours after the initial dose of study medication and daily evaluations were made thereafter. Adult patients were included in the onset analysis if they received an initial FP dose of 200 microg. Pediatric patients who received an initial FP dose of 100 microg were also included. Onset of effect was evaluated by 1) examining the timepoints at which statistically significant differences were observed between FP and placebo in mean change from baseline for total nasal symptom score (TNSS); and by 2) using a binary probability model of success/failure to determine statistically significant differences from placebo. RESULTS: Twenty-two studies met the criteria to evaluate onset of therapeutic effect; 3,605 patients with rhinitis received FP and 2,271 patients received placebo. This database represents the largest compilation of data ever assembled to determine the onset of therapeutic effect of a corticosteroid nasal spray. Two studies used a "park design" to examine onset of effect; statistically significant differences in TNSS favoring FP were achieved at hours 2 to 4 and at hour 12, respectively. Using a binary probability model of success/failure for analysis of TNSS in the remaining 20 studies not specifically designed to evaluate onset of effect, numerically greater improvements in TNSS for FP compared with placebo were found in 19 of the 20 studies within 12 hours of the administration of the first dose (P < .001). Pairwise comparisons showed statistically significant improvement for TNSS within 12 hours postdose in five of the studies for FP compared with placebo and in none for placebo compared with FP. CONCLUSIONS: Onset of therapeutic effect occurs within 12 hours, and as early as 2 to 4 hours in some patients, after administration of the first dose of FP aqueous nasal spray.