Therapeutic Equivalence and Early Onset of Action of a Novel Water-Soluble Budesonide Nasal Spray (budesolv 10) Compared to Rhinocort® Aqua 64 in Patients Suffering from Grass Pollen Induced Allergic Rhinitis with or Without Asthma

Intranasal corticosteroids are deemed the most effective treatment for allergic rhinitis. Purpose of this single site study was to evaluate the non-inferiority of an aqueous solution of Budesonide (“Budesolv 10μg”; six-fold lower dose than the active comparator) to Rhinocort® aqua 64μg in patients with grass pollen allergy on day 8 of treatment and to determine onset of action after the first application on day 1. In this randomised DBPC three-way crossover pivotal phase III trial, adult subjects with clinically proven grass pollen allergy with or without controlled asthma were included. Patients received placebo, Budesolv and Rhinocort® once daily for eight days with a washout period of three weeks between treatment blocks. Allergic symptoms were induced during 6-h allergen challenges in the Vienna Challenge Chamber at beginning and end of each 8-day treatment period. On day 1, the first dose was applied after nearly two hours of allergen challenge to evaluate the onset of action of either treatment. Primary endpoint was the mean total nasal symptom score (TNSS; sum of obstruction, itch, sneeze and rhinorrhoea assessed on a categorical scale from 0 to 3) between 2 and 6 hours of allergen challenge on day 8. Secondary endpoints included onset of action, ocular and asthma symptoms and objective measures of nasal secretion and nasal obstruction. For the primary criterion, a 95% confidence interval (CI) was calculated for difference in means between the two active treatments. Non-inferiority was stated if the upper limit of the CI did not exceed 115% of the reference. Onset of action was defined as first time point when the difference in TNSS change from baseline between active treatment and placebo was p<0.05. The protocol was approved by the Austrian CA and EC. 75 patients concluded the study per protocol. Mean TNSS score sums on day 8 were 4.98, 5.05 and 7.48 for Budesolv, Rhinocort® and placebo, thereby proving non-inferiority. A significant difference between Budesolv and placebo on day 1 was shown for TNSS 2.45 hours and for total asthma score 2 hours after first dose. For ocular symptoms there was no difference between active and placebo on day 1. On day 8 Budesolv 10μg was significantly better than placebo for all parameters evaluated. Non-inferiority of Budesolv compared to Rhinocort® was shown on day 8 of treatment. Early onset of action within 3 hours after first dose was evident for Budesolv only.