Safety, tolerability and efficacy of indacaterol, a novel once-daily beta(2)-agonist, in patients with COPD: a 28-day randomised, placebo controlled clinical trial.

In patients with chronic obstructive pulmonary disease (COPD) classified as moderate onwards, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines recommend regular treatment with one or more long-acting bronchodilators, such as beta(2)-agonists or anticholinergics. In contrast to currently available long-acting beta(2)-agonists, which have a duration of action of 12 h, indacaterol has demonstrated effective 24-h bronchodilation on once-daily dosing. A double-blind, randomised, placebo-controlled study was conducted to compare the safety, tolerability and efficacy of indacaterol with that of placebo, over a 28-day period, in patients with moderate COPD (as defined by GOLD 2001 criteria; equivalent to moderate-to-severe COPD in the GOLD 2005 criteria). Patients were randomised 2:2:1 to receive indacaterol 400 microg or 800 microg or placebo once-daily (between 07:00 and 11:00 h) via a single-dose dry-powder inhaler for 28 days. Assessments included monitoring of adverse events (AEs), blood chemistry (including serum potassium and blood glucose), vital signs (blood pressure and heart rate), electrocardiograms and spirometry. One hundred and sixty-three patients were randomised, with 155 (95%) completing the study. There were no statistically significant differences between treatment groups in the overall incidence of AEs, with AEs reported by 35%, 51% and 25% of patients in the indacaterol 400 microg, 800 microg and placebo groups, respectively. The majority of AEs were mild or moderate in severity, and there were no study-drug related serious AEs. There were no statistically significant differences between indacaterol groups and placebo in mean pulse rate and QTc interval, and isolated statistically significant (p<0.05) treatment-placebo differences in mean blood pressure, blood glucose and serum potassium. There was a statistically significant improvement in FEV(1) vs placebo at all post-baseline timepoints for both indacaterol treatment groups; 30 min post-dose, adjusted mean+/-SE FEV(1) indacaterol-placebo differences were: Day 1, 220+/-36 ml and 210+/-36 ml; Day 14, 320+/-50 ml and 270+/-50 ml; Day 28, 260+/-61 ml and 200+/-61 ml for 400 and 800 microg, respectively (all p<0.01 vs placebo). Bronchodilation was still apparent after 24h, with pre-dose (i.e. trough) adjusted mean+/-SE FEV(1) indacaterol-placebo differences of: Day 14, 230+/-44 ml and 210+/-44 ml; Day 28, 220+/-49 ml and 210+/-49 ml for indacaterol 400 and 800 microg, respectively (all p<0.0001 vs placebo). Once-daily indacaterol was well tolerated at doses up to 800 microg with a good overall safety profile. There was no statistical difference at any dose between the safety of indacaterol and placebo. Furthermore, this study supports the previously demonstrated 24-h bronchodilator efficacy of indacaterol.