Background: Indacaterol is a novel, inhaled, once-daily beta2-agonist.

Objective: To investigate the safety and tolerability of indacaterol at doses of 400 and 800 microg/d.

Methods: Randomized, double-blind, placebo-controlled, parallel-group, multicenter, 28-day study. Patients with persistent asthma (forced expiratory volume in 1 second [FEV1] > or =-60% predicted, < or =1,600 microg of beclomethasone dipropionate or equivalent daily) received indacaterol, 400 microg (n = 59) or 800 microg (n = 59), or placebo (n = 26) once daily via a single-dose dry powder inhaler. Safety assessments were performed before and after dosing on days 1, 14, and 28, with particular attention to key beta2-agonist safety variables.

Results: A total of 144 patients were randomized, with 135 (93.8%) completing the study. Indacaterol was well tolerated: the incidence of adverse events (AEs) was similar between the active and placebo groups, and AEs, when they occurred, were mild or moderate for most (98.2%). There was no dose-response relationship between indacaterol and the incidence of AEs (400 microg, 40.7%; 800 microg, 37.3%; and placebo, 38.5%). Few AEs considered as beta2-agonist class effects occurred (none leading to withdrawal). Small differences between indacaterol and placebo in mean serum potassium (< or =-0.29 mmol/L) and glucose (< or =0.93 mmol/L) levels were occasionally statistically significant (P < .05) but not regarded as clinically meaningful. As expected for a beta2-agonist, there was some indication of a trend in QTc prolongation with increasing exposure (maximum mean change, 8.9 milliseconds; P < .05 vs placebo). Significant increases in FEV1 (P < .05) were seen at all postbaseline time points for both indacaterol doses vs placebo, with indacaterol-placebo differences 30 minutes after dosing of 0.21 to 0.25 L and before dosing on days 14 and 28 (approximately 24 hours after the previous dose) of 0.15 to 0.23 L.

Conclusion: Indacaterol had a good overall safety profile and was well tolerated at both doses, with predose FEV1 results on days 14 and 28 indicating 24-hour bronchodilator efficacy.