Lung function with aclidinium/formoterol fixed-dose combination: Pooled analysis of two phase III studies in COPD

Background: Combining two bronchodilators with different mechanisms of action may provide additional benefits versus monotherapy in patients with COPD. Aim: To assess the effect of twice-daily (BID) aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) on bronchodilation in patients with moderate to severe COPD by pooling data from the ACLIFORM (NCT01462942) and AUGMENT (NCT01437397) trials in a pre-specified analysis. Method: Patients were randomised to aclidinium/formoterol FDC 400/12 or 400/6 µg, aclidinium 400 µg, formoterol 12 µg or placebo BID. Co-primary endpoints were change from baseline in 1-hour morning post-dose FEV1 versus aclidinium and morning pre-dose (trough) FEV1 versus formoterol at Week 24. Results: The intent-to-treat population included 3394 patients (mean age: 63.5 years; % predicted FEV1: 48.4). The FDCs produced significant improvements in the co-primary endpoints at the first time point assessed; these improvements were sustained at Week 24 (table). Bronchodilation was significant at the first time point post-dose (Day 1, 5 min post-dose: 108–120 mL vs placebo, p<0.001). Peak FEV1 was significantly improved with the FDCs versus placebo and both monotherapies at each visit (all p<0.001). Conclusion: Both doses of aclidinium/formoterol FDC demonstrated rapid, sustained improvements in lung function over 24 weeks versus placebo and the monotherapies in patients with COPD.