QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease

Background This randomised, double-blind, placebo controlled, four-period crossover study assessed the efficacy and safety of once-daily QVA149, a dual bronchodilator consisting of the long-acting beta(2)-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods Patients (N=154) were randomly assigned to receive QVA149 (indacaterol/NVA237) 300/50 mu g, indacaterol 300 mu g, indacaterol 600 mu g, or placebo, once daily for 7 days with a 7-day washout period between each treatment. The primary endpoint was trough forced expiratory volume in 1 s (FEV(1)) (mean of 23 h 15 min and 23 h 45 min post-dose values) on day 7. Other endpoints included trough FEV(1) on day 1, individual time point FEV(1) and monitoring and recording of all adverse events. Results A total of 135 (87.7%) patients completed the study (all randomly assigned patients: mean age 61.7 years, 61.4% male, post-bronchodilator FEV(1) 52.2% predicted, FEV(1)/forced vital capacity 47.6%). The estimated treatment difference (95% CI) for trough FEV(1) on day 7 between QVA149 and placebo was 226 ml (192 to 260; p<0.001). The estimated treatment difference between QVA149 and indacaterol 300 and 600 mg was 123 ml (89 to 157; p<0.001) and 117 ml (83 to 150; p<0.001), respectively. The improvements in mean trough FEV(1) exceeded the predefined minimal clinically important differences of 100-140 ml for QVA149 versus placebo and indacaterol. Similar results were observed on day 1. All treatments were well tolerated. Conclusions QVA149 demonstrated rapid and sustained bronchodilation with significant improvements compared with indacaterol monotherapy and placebo in patients with COPD.