Study AMPLIFY Confirmed Safety and Efficacy of Fixed Combination Aclidinium/Formoterol in COPD Therapy
The randomized double-blind phase III AMPLIFY study compared the efficacy of a fixed combination of formoterol/aclidinium with monotherapy of the individual components or with tiotropium in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).
Introduction
For patients with stable COPD and persistent symptoms or a high risk of exacerbations, combined therapy with a long-acting muscarinic receptor antagonist and a long-acting β2-agonist (LAMA/LABA) is recommended as maintenance therapy. The efficacy of the combination of aclidinium bromide (AB) and formoterol fumarate (FF) compared to placebo and the individual components of this combination in monotherapy has been confirmed previously, but this study included the frequently used tiotropium (TIO) among the comparators.
Methodology and Objectives of the Study
AMPLIFY was a 24-week double-blind study that randomized symptomatic patients with COPD (CAT score [COPD assessment test] ≥ 10) into 4 arms. In the individual arms, patients received either AB/FF fixed combination 400/12 µg twice daily, AB 400 µg twice daily, FF 12 µg twice daily, or TIO 18 µg once daily.
The primary objectives included the change in forced expiratory volume in one second (FEV1) at week 24 compared to baseline in two measurements: one hour post-dose (AB/FF vs. AB) and pre-dose (AB/FF vs. FF). Noninferiority of AB vs. TIO was also assessed in pre-dose FEV1. Additionally, symptoms during the night and early morning and the normalized area under the curve AUC0–3/3 hrFEV1 were evaluated. A subset of patients participated in a sub-study where participants underwent 24-hour serial spirometry.
Results
A total of 1594 patients were randomized, with 566 participating in the sub-study. At week 24, FEV1 one hour post-dose significantly improved in the AB/FF arm compared to AB, FF, and TIO arms (differences between treatments: 84, 84, and 92 ml; p < 0.0001 for all comparisons of AB/FF with comparators). The AB/FF fixed combination significantly improved pre-dose FEV1 compared to FF (difference 55 ml; p < 0.001) and AB was noninferior to TIO.
Significant improvement in AUC0-3/3 hrFEV1 was observed in the AB/FF arm compared to all other groups (p < 0.0001), and significant improvement in morning symptoms compared to TIO. The 24-hour spirometry showed significantly greater improvement in AUC12–24/12 hr for AB/FF compared to all comparators, and at week 24 in AUC0–24/24 hr compared to FF or TIO.
The incidence of treatment-related adverse events was similar across all groups.
Summary and Conclusion
In patients with moderate to very severe symptomatic COPD, the fixed combination of aclidinium/formoterol administered twice daily significantly improved lung function compared to monotherapy with the individual components or tiotropium. The fixed combination also significantly improved morning COPD symptoms compared to tiotropium. The results support the sustainable efficacy of the fixed combination over 24 hours and demonstrate that it provides better control of nighttime and morning COPD symptoms compared to monotherapy.
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Source: Sethi S., Kerwin E., Watz H. et al. 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. Int J Chron Obstruct Pulmon Dis 2019; 14: 667–682, doi: 10.2147/COPD.S189138.
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