This dose-ranging study assessed the bronchodilator efficacy and tolerability of indacaterol, a novel once-daily inhaled β2-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 ⩾1.0 L; FEV1/FVC <70%) were randomized to receive indacaterol 50, 100, 200 or 400 μg or placebo via multi-dose dry powder inhaler, or indacaterol 400 μg 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 μg 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 AUC22–24h) on Day 1.
Clinically relevant improvements versus placebo in FEV1 AUC22–24h were seen for 400 and 200 μg 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 μg 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 β2-agonist bronchodilator. Indacaterol demonstrated a good overall safety and tolerability profile.
