Sustained 24-hour efficacy of once daily indacaterol (300 μg) in patients with chronic obstructive pulmonary disease: A randomized, crossover study

Purpose: Indacaterol is a novel, once daily, inhaled ultra-long-acting beta(2)-agonist for the treatment of chronic obstructive pulmonary disease (COPD). Here we compared the 24-h spirometry profile of once daily indacaterol 300 mu g with that of placebo and twice daily salmeterol 50 mu g in patients with COPD. Methods: This randomized, multicenter, placebo-controlled, crossover study comprised three 14-day treatment periods (with 14-day washouts). Patients (male/female >= 40 years) with moderate-to-severe COPD were randomized to receive double-blind indacaterol 300 mu g or placebo once daily, or open-label salmeterol 50 mu g twice daily. The primary outcome measure was 24-h post-dose (trough) FEV1 (mean of FEV1 at 23 h 10 min and 23 h 45 min post-indacaterol dose) after 14 days. FEV1 was assessed at multiple time points on Days 1 and 14 of each treatment period. Safety and tolerability were also monitored. Results: Of 68 randomized patients, 61 completed. Trough FEV1 (primary endpoint) on Day 14 for indacaterol was 200 mL higher than placebo (p < 0.001), exceeding the prespecified minimum clinically important difference (120 mL), and was 90 mL higher than for salmeterol (p = 0.011). After Day 1, trough FEV1 for indacaterol was 150 mL higher than placebo (p < 0.001). Indacaterol provided superior bronchodilation compared with placebo (p < 0.001) across the full 24-h assessment period on Days 1 and 14. In addition, on both days, indacaterol provided superior FEV1 compared with salmeterol (p < 0.05) at many post-baseline time points, including 5 min post-dose. All treatments were well tolerated. Conclusions: Once daily indacaterol 300 mu g produced effective sustained 24-h bronchodilation from the first dose, an efficacy profile superior to placebo and twice daily salmeterol. Given its effective bronchodilation with once daily dosing, indacaterol is likely to be a useful treatment option for patients with moderate-to-severe COPD. (C) 2010 Elsevier Ltd. All rights reserved.