A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison

This dose-ranging study assessed the bronchodilator efficacy and tolerability of indacaterol, a novel once-daily inhaled beta(2)-agonist, in subjects clinically diagnosed with COPD. Comparative data with tiotropium were collected. In the double-blind, core period of the study, 635 subjects with COPD (prebronchodilator FEV1 >= 40% of predicted and >= 1.0L; FEV1/FVC < 70%) were randomized to receive indacaterol 50, 100, 200 or 400 mu g or placebo via multi-dose dry powder inhaler, or indacaterol 400 mu g via single-dose dry powder inhaler, once daily for 7 days. After completing double-blind treatment and washout, a subset of subjects from each treatment group entered an open-label extension and received tiotropium 18 mu g once daily for 8 days. The primary efficacy variable was the trough bronchodilator effect: standardized area under the FEV1 curve between 22 and 24 h post-dose (FEV1 AUC(22-24h)) on Day 1. Clinically relevant improvements versus placebo in FEV1 AUC(22-24h) were seen for 400 and 200 mu g doses on Day 1 and all doses on Day 7. All indacaterol doses significantly (P < 0.05) increased FEV1 from 5 min to 24 h post-dose; the 400 and 200 mu g doses were most effective. All doses were well tolerated. Indacaterol trough FEV1 levels compared favorably with the improvement seen by Day 8 in subjects treated with tiotropium in the open-label extension. The results confirm that indacaterol has a 24-h duration of bronchodilator effect and a fast onset of action in COPD and suggest that indacaterol could be an effective once-daily inhaled beta(2)-agonist bronchodilator. Indacaterol demonstrated a good overall safety and tolerability profile. (c) 2008 Elsevier Ltd. All rights reserved.