Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study

Indacaterol is a novel, once-daily beta(2)-agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation. A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol. A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 mu g via multi-dose dry-powder inhaler (MDDPI; Certihaler((TM))), indacaterol 400 mu g via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored. All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV1) from 22 to 24 h postdose (P <= 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment-placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 mu g via MDDPI and 400 mu g via SDDPI, respectively. All doses increased mean FEV1 (P < 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild-to-moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders. Once-daily dosing with indacaterol provided sustained 24-h bronchodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 mu g appears the optimum dose, offering the best efficacy/safety balance.