No abstract

Poster sessions A128Thorax 2012;67(Suppl 2):A1-A204 Background Topical intranasal steroids are widely considered to be the most efficacious pharmacotherapy for the treatment of allergic rhinitis, and yet, for many, symptoms still remain troublesome. We hypothesise that the residual symptoms are a result of nasal neuronal hyperresponsiveness during the pollen season and should be ameliorated by a topical intranasal TRPV1 antagonist. SB705498 is a selective TRPV1 antagonist shown to produce significant inhibition in animal and human models involving nasal sensory nerves. Methods The study involved 70, male and female, subjects with proven rhinitis in a randomised, double-blind, placebo-controlled, 3-way incomplete block crossover design in a well validated Allergen Challenge Chamber paradigm in Vienna. Subjects received Placebo, FP (200ug), SB705498 (12mg), or FP+498. Subjects were dosed for 8 days, within the pollen season, before being exposed to a chamber challenge on the 8 th day. TNSS was the primary endpoint recorded for the 4 hours in the chamber. The comparisons of interest were FP+498 vs. FP, and 498 vs. Placebo. Additional endpoints consisted of symptoms over the 8 days of dosing, Active Anterior Rhinomanometry, Rhinoconjunctivitis QLQ, PK and tolerability. Each period was separated by 14-20 days. Results There was no evidence of a decrease in symptoms with FP+498 compared to FP alone, or for 498 compared to placebo. Statistically significant and clinically relevant reductions in TNSS compared with Placebo were observed at all time points during the challenge for FP and FP+498. The mean (95% CI) reduction in weighted mean TNSS was -2.94 (-3.38, -2.50) for FP alone and-2.28 (-2.79, -1.78) for the combination.

The threshold UV erythema suppression model assessed in this study could not distinguish between oral prednisolone and placebo. This UV-erythema suppression test system is not promising as a model to test the anti-inflammatory potency of systemic steroids.