Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients

NVA237 is a once-daily inhaled long-acting muscarinic antagonist in development for the treatment of COPD. This randomized, double-blind, placebo-controlled, four-period, incomplete block crossover study, with open-label active comparator (tiotropium), assessed the efficacy and safety of NVA237. Patients (>= 40 years; smoking history >= 10 pack-years) with stable moderate-to-severe COPD (post-bronchodilator FEV1 >= 30% and <80% predicted, FEV1/FVC < 0.7) received NVA237 12.5, 25, 50 or 100 mu g, placebo, or tiotropium 18 mu g once-daily for 7 days. The primary endpoint was mean trough (23-24 h post-dose) FEV1 on Day 7. Secondary endpoints included mean trough FEV1 on Day 1, and FEV1 and FVC at individual time points post-dose on Days 1 and 7. 83 patients (mean age 64.4 years; male 83.1%; mean COPD duration 6.7 years; mean post-bronchodilator FEV1 1.5 L/52.7% predicted) were randomized; 78 completed. Mean trough FEV1 on Day 7 and Day 1 was significantly higher with all active treatments versus placebo (p < 0.05). NVA237 50 mu g, 100 mu g and tiotropium showed clinically relevant improvements versus placebo on Day 7 (differences of 131, 142 and 127 mL, respectively; p < 0.0001) and 1 (differences of 121, 135 and 112 mL, respectively; p < 0.0001). On Day 1, but not Day 7, FEV1 was significantly higher (p < 0.05) with NVA237 50 and 100 mu g versus tiotropium from 5 min up to 2 and 4 h post-dose, respectively. All doses of NVA237 and tiotropium were well tolerated. NVA237 once-daily was effective and well tolerated versus placebo, and demonstrated rapid and sustained 24-h bronchodilation. (ClinicalTrials.gov Identifier: NCT00501852). (C) 2010 Published by Elsevier Ltd.