AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD

摘要

Background: AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677). Methods: In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 μg, AB 400 μg, or FF 12 μg, or once-daily TIO 18 μg. Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEVsub1/sub (AB/FF vs AB) and in pre-dose (trough) FEVsub1/sub (AB/FF vs FF). Non-inferiority of AB vs TIO in pre-dose FEVsub1/sub was also an objective. Normalized area under the curve (AUC)sub0–3/3 h/sub FEVsub1/sub and nighttime and early morning symptoms were also assessed. A subgroup participated in a 24-hour serial spirometry sub-study. Results: A total of 1,594 patients were randomized; 566 entered the sub-study. At week 24, 1-hour post-dose FEVsub1/sub significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P 0.0001). AB/FF significantly improved trough FEVsub1/sub vs FF (55 mL, P 0.001) and AB was non-inferior to TIO. AB/FF significantly improved AUCsub0–3/3 h/sub FEVsub1/sub vs all comparators ( P 0.0001) and provided significant improvements in early morning symptoms vs TIO. The 24-hour spirometry demonstrated significantly greater improvements with AB/FF in AUCsub12–24/12 h/sub vs all comparators, and in AUCsub0–24/24 h/sub vs FF or TIO at week 24. Conclusion: In patients with moderate-to-very severe symptomatic COPD, twice-daily AB/FF significantly improved lung function vs monocomponents and TIO, and early morning symptom control vs TIO.