Safety of indacaterol in the treatment of patients with COPD

Abstract

James F Donohue1, Dave Singh2, Oliver Kornmann3, David Lawrence4, Cheryl Lassen4, Benjamin Kramer5 1University of North Carolina, Chapel Hill, NC, USA; 2University of Manchester, Medicines Evaluation Unit, Manchester, UK; 3IKF Pneumologie GmbH and Co KG, Clinical Research Centre Respiratory Diseases, Frankfurt, Germany; 4Novartis Horsham Research Centre, Horsham, UK; 5Novartis Pharmaceuticals Inc, East Hanover, New Jersey, USA Purpose: Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting ß2-agonist for chronic obstructive pulmonary disease (COPD). Patients and methods: Data were pooled from clinical studies of 3–12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 µg (n = 449), 150 µg (n = 2611), 300 µg (n = 1157), or 600 µg once daily (n = 547); formoterol 12 µg twice daily (n = 556); salmeterol 50 µg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 µg once daily, given open label or blinded (n = 1214). Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs. Results: The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments. The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo. COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo. Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses. Notable values for vital signs and measures of systemic ß2-adrenoceptor activity were rare with indacaterol. The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07–0.660], P = 0.008). Conclusion: Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD. Keywords: indacaterol, safety, tolerability, formoterol, salmeterol, tiotropium