Dovepress Clinical data for once-daily indacaterol At the time of writing, several thousands of patients with COPD have received indacaterol in various doses for up to 52 weeks of treatment during the Phase II and III clinical program. Early clinical studies suggested that indacaterol produces rapid (within 5 minutes) and sustained (for at least 24 hours) bronchodilation in patients with various degrees of airflow obstruction.35,36 Further, a study by Beier et al37 confirmed that a single dose of indacaterol 300 mcg provided a greater effect on airflow obstruction and resting hyperin- flation (inspiratory capacity) in patients with COPD than twice-daily formoterol 12 mcg.37 In the randomized, controlled Phase III COPD trials investigating the effects of treatment with 150 mcg or 300 mcg indacaterol once daily for up to 52 weeks’ duration, indacaterol effectively improved numerous clinical outcomes over placebo, including trough FEV1, symptom control, dyspnea, quality of life, and exacerbations.38–40 However, the Phase III studies also incorporated several active compara- tor drugs, including the twice-daily LABAs formoterol and salmeterol and the once-daily anticholinergic tiotropium. In a 2-week, open-label comparison study of indacaterol 300 mcg once daily versus salmeterol 50 mcg twice daily, trough FEV1 on day 14 for indacaterol was 90 mL higher than for salmeterol (P = 0.011). This was also accompanied by superior improvements in resting inspiratory capacity across a full 24-hour assessment period on day 14, reaching statistical significance at most post-dose timepoints.41 Compared with salmeterol 50 mcg twice daily, inda- caterol 150 mcg once daily was superior in improving trough FEV1 after 12 weeks and 26 weeks (differences +60 mL and +70 mL, respectively, P , 0.001), quality of life, dysp- nea, and need for additional rescue medication in a random- ized, double-blind, comparison study.39 Superior clinical efficacy of 150 mcg indacaterol once daily versus salmeterol twice daily was also confirmed in a double-blind, 12-week comparison study.42 A long-term comparison of indacaterol 300 mcg once daily over 52 weeks showed superior effects of indacaterol over formoterol 12 mcg twice daily on lung function (trough FEV1), dyspnea, and rescue medication usage.43 In a pooled analysis, it appeared that 150 mcg indacaterol once daily also provided superior benefits on trough FEV1 after 12 weeks of treatment versus formoterol 12 mcg twice daily, regardless of concomitant use of inhaled corticosteroids.44 During a 26-week randomized comparison trial, inda- caterol 150 mcg or 300 mcg once daily was compared with International Journal of COPD 2011:6 Long-acting β-adrenoceptor agonists and COPD placebo and open-label tiotropium 18 mcg once daily over 26 weeks.45 Trough FEV1 at week 12 increased versus placebo by 180 mL with both indacaterol doses and by 140 mL with tiotropium (all P , 0.001). At week 12 and week 26, there were also significant treatment differences between indacaterol at both doses and tiotropium (+40–50 mL favor- ing indacaterol), when tested for superiority (P , 0.05, all comparisons), although the interpretability of these data may be complicated by the fact that tiotropium was administered open label. Further clinically relevant improvements were observed with indacaterol versus placebo for dyspnea and health-related quality of life. However, a fully (third-party) blinded, randomized, double-blinded, crossover clinical comparison of the effects of indacaterol 150 mcg and 300 mcg once daily versus tiotropium 18 mcg once daily or matching placebo proved noninferiority for both doses of indacaterol in regard to trough FEV1 after 14 days of treatment compared with tiotropium 18 mcg, with mean trough FEV1 values again favoring indacaterol 150 mcg (+50 mL vs tiotropium) and 300 mcg (+30 mL vs tiotropium). Although superiority was not proven statistically, these data nevertheless altogether indicate that indacaterol provides at least equipotent bronchodilation after 14 days compared with tiotropium.46 Finally, a further blinded comparison of indacaterol 150 mcg with tiotropium 18 mcg once daily showed com- parable effects on trough FEV1 after 12 weeks (1.44 L for indacaterol vs 1.43 L for tiotropium, P , 0.001 for noninferi- ority), with additional benefits for indacaterol over tiotropium in regard to dyspnea, health-related quality of life, and rescue medication use.47 Pooled analyses and subgroups Pooled analyses, including some of the aforementioned clinical trials, were published during the American Thoracic Society 2010 annual meeting. These data demonstrated that indacaterol 150 mcg or 300 mcg once daily administered over 3–6 months provides significant and clinically mean- ingful improvement of symptoms, health-related quality of life, rescue medication use, and exacerbation rates in moderate-to-severe COPD patients.48,49 Further, it was shown that longer-term beneficial effects of indacaterol were not dependent on age, concomitant inhaled corticosteroid use, and baseline bronchodilator reversibility.44,50,51 Safety Safety studies with indacaterol addressed the occurrence of adverse events and serious adverse events, cardiovascular submit your manuscript | www.dovepress.com Dovepress 239