Beier and Beeh safety, and known class effects from β-agonists due to systemic absorption of drug, potentially leading to tachycardia, palpitations, changes in electrocardiogram parameters (eg, QT prolongation), hypokalemia, increase in blood glucose levels, and adverse events like tremor or headache. Phase II studies Three multiple-dose Phase II trials primarily evaluating safety and tolerability of indacaterol have as yet been fully published, two in asthma52,53 and one in COPD.54 These three trials incorporated a treatment duration of 28 days. However, trials used different dosages of indacaterol, and indacaterol was delivered in a multiple-dose dry powder inhaler, which differs from the currently marketed single- dose dry powder inhaler device. In studies by Yang et al53 and Beier et al54 indacaterol at once-daily doses of 400 mcg and 800 mcg from single-dose dry powder inhaler was used, whereas Chuchalin et al52 evaluated indacaterol at dosages of 200 mcg, 400 mcg, or 600 mcg daily. In all studies, the overall incidence of adverse events was similar for active treatment and placebo groups, and there was no dose-related increase in the incidence of adverse events. The most common adverse event associated with indacaterol use was cough, which was reported in 16.9% and 15.3% of patients in the indacaterol 400 mcg and 800 mcg groups, respectively, in the study by Yang et al;53 in 8.1%, 17.1%, and 10.3% of patients in the indacaterol 600 mcg, 400 mcg, and 200 mcg groups, respectively, in the study by Chuchalin et al;52 and in 14.7% and 28.4% of patients in the 400 mcg and 800 mcg groups, respectively, in the study by Beier et al.54 For the typical class effects of β-agonists, only modest effects were observed. Although Yang et al53 reported small changes in postdose serum potassium and glucose levels of asthmatic patients exposed to indacaterol 400 mcg or 800 mcg, no effect on these parameters was observed in the study by Beier et al54 using the same doses in COPD patients. In the study by Chuchalin et al52 in asthmatics, no effect of once-daily indacaterol 200 mcg, 400 mcg, and 600 mcg on potassium and glucose levels was observed. In this study, there were also no changes in pulse rate, blood pressure, or mean QTc interval after 28 days’ exposure to indacaterol. However, there was a small, statistically significant increase of the QTc interval (8.9 ms) and pulse rate (4.9 beats per minute) with the 800 mcg dose (n = 59) on day 28 in the study byYang et al53 but these changes were numerically small and not clinically significant. Again, none of these effects 240 submit your manuscript | www.dovepress.com Dovepress Dovepress was observed by Beier et al54 in the study using indacaterol 400 mcg and 800 mcg once daily in COPD patients. The effect of indacaterol at dosages up to 600 mcg once daily over 14 days on QTc values has been studied in a thorough QT study in healthy subjects. All doses of indacaterol had no effect on mean QTc values, and changes were within the regulatory safety margin.55 Finally, inhalation of supratherapeutic single doses of indacaterol up to 3000 mcg in COPD patients revealed only minor systemic effects.56 Phase III trials In a 12-week trial investigating 150 mcg indacaterol versus placebo for 12 weeks,40 the incidence of any adverse event was comparable for indacaterol and placebo (indacaterol n = 104, 49.3%; placebo n = 96, 46.8%). There were no cardiac safety issues. No patient had a prolongation of the QTc interval beyond 500 msec absolute or .60 msec increase from baseline, and no increase of pulse rate was observed. During a further 26-week comparison trial, the frequency of adverse events was comparable for indacaterol 150 mcg and 300 mcg with open-label tiotropium and placebo. Similarily, the overall proportion of patients with an increase in QTcF of 30–60 msec or .60 msec was low and comparable with tiotropium and placebo.57 Finally, during the large-scale comparator trial with indacaterol 300 mcg and 600 mcg versus formoterol 12 mcg twice daily and placebo over 1 year, adverse events and severe adverse events occurred in a similar frequency for both doses of indacaterol and placebo. Again, the overall propor- tion of patients with an increase in QTcF of 30–60 msec or .60 msec was low and comparable with formoterol and placebo. Further, indacaterol at both doses did not affect mean serum potassium at week 52, mean QTc values, or average pulse rate.43 Chapman et al38 recently reported on the safety of inda- caterol 150 mcg and 300 mcg once daily versus placebo during the 26-week extension phase of the 26-week open- label tiotropium comparison study, thereby providing data over a total duration of 52 weeks. In their analysis, adverse events occurred in 76%, 77%, and 68% of subjects receiv- ing indacaterol 150 µg, 300 µg, and placebo, respectively, whereas serious adverse events occurred in 10.4%, 12.3%, and 10.5%, respectively. There were no clinically significant effects with indacaterol at both doses on QTc interval or potassium or glucose levels. Finally, Worth et al58 specifically reported on the cardio- and cerebrovascular safety of indacaterol 150 mcg and International Journal of COPD 2011:6