The 24 Hour Lung Function Time Profile of Olodaterol Once Daily Versus Placebo and Tiotropium in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Background: Olodaterol is a once-daily long-acting β2-agonist being investigated for the treatment of chronic obstructive pulmonary disease, with ≥ 24 hour bronchodilator activity.Methods: Two replicate, randomized, double-blind, four-way crossover (6-week treatment periods), active (tiotropium 18 µg via HandiHaler®)-and placebo-controlled trials were conducted to evaluate the 24 hour forced expiratory volume in 1 second (FEV1) profile of olodaterol (5 and 10 µg) once daily (via Respimat®).Patients continued with inhaled corticosteroids and xanthines.Spirometry was performed at baseline and over the entire 24 hour post-dose period at week 6 of each treatment phase.Co-primary end points were change from study baseline (response) in FEV1 area under the curve from 0-12 hours (AUC0-12) and FEV1 AUC from 12-24 hours (AUC12-24); key secondary end point was FEV1 AUC from 0-24 hours response.Results: In study 1222.39,there was a significant difference from placebo in FEV1 AUC0-12 and AUC12-24 responses (P<0.0001) with olodaterol 5 µg (0.185 and 0.131 L) and 10 µg (0.207 and 0.178 L) at 6 weeks; similar results were observed for tiotropium (0.173 and 0.123 L).In study 1222.40,responses were 0.197 and 0.153 L with olodaterol 5 µg, 0.221 and 0.170 L with 10 µg, and 0.221 and 0.164 L with tiotropium versus placebo (P<0.0001).Incidence of adverse events was comparable across treatments.Conclusions: These data confirm the 24 hour lung-function efficacy profile of once-daily olodaterol, with FEV1 responses comparable to tiotropium.