Medicina Pulmonar e Respiratória

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

Abstract

Peter Lange, Joseph-Leon Aumann, Alan Hamilton, Kay Tetzlaff, Naitee Ting and Eric Derom

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.