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.

Autor: Sethi S; Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA, ssethi@buffalo.edu., Kerwin E; Clinical Research Institute, Medford, OR, USA., Watz H; Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany., Ferguson GT; Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA., Mroz RM; Centrum Medycyny Oddechowej, Białystok, Poland.; Medical University of Białystok, Białystok, Poland., Segarra R; AstraZeneca, Barcelona, Spain., Molins E; AstraZeneca, Barcelona, Spain., Jarreta D; AstraZeneca, Barcelona, Spain., Garcia Gil E; AstraZeneca, Barcelona, Spain.
Jazyk: angličtina
Zdroj: International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2019 Mar 22; Vol. 14, pp. 667-682. Date of Electronic Publication: 2019 Mar 22 (Print Publication: 2019).
DOI: 10.2147/COPD.S189138
Abstrakt: 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 FEV 1 (AB/FF vs AB) and in pre-dose (trough) FEV 1 (AB/FF vs FF). Non-inferiority of AB vs TIO in pre-dose FEV 1 was also an objective. Normalized area under the curve (AUC) 0-3/3 h FEV 1 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 FEV 1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P <0.0001). AB/FF significantly improved trough FEV 1 vs FF (55 mL, P <0.001) and AB was non-inferior to TIO. AB/FF significantly improved AUC 0-3/3 h FEV 1 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 AUC 12-24/12 h vs all comparators, and in AUC 0-24/24 h 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.
Competing Interests: Disclosure SS has received grants from AstraZeneca, Dey, and Pearl Therapeutics. He has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cempra, CSL Behring, Forest, GlaxoSmithKline, Merck, Pearl Therapeutics, Pulmonx, Reckitt Benckiser, Sunovion, and Theravance. EK has served on advisory boards, speaker panels, or received travel reimbursement from Amphastar, AstraZeneca, GlaxoSmithKline, Mylan, Novartis, Oriel, Pearl Therapeutics, Sunovion, Teva, and Theravance. He has conducted multicenter clinical trials for ~ 40 pharmaceutical companies. HW has received honoraria for consultancies, lectures, and travel support to attend scientific congresses from Almirall, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Takeda. His institution received investigator fees for participation in clinical trials from Almirall, AstraZeneca, Bayer Health Care, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Roche, Sanofi Aventis, and Takeda. GTF reports consulting and advisory board participation for AstraZeneca, Boehringer Ingelheim, Forest Laboratories, Novartis, Pearl Therapeutics, Sunovion, and Verona Pharma; consulting fees from Receptos; speaking engagements for AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, Pearl Therapeutics, and Sunovion; and research grants from AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Therapeutics, Sanofi, Sunovion, and Theravance Biopharma. RMM has received consulting fees, speaker’s fees, and travel expenses from Boehringer Ingelheim and has also received compensation for participating in advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim, and Novartis. Furthermore, RMM has received compensation for participation in multicenter clinical trials in the past 5 years from several companies including Almirall, AstraZeneca, Boehringer Ingelheim, GSK, Merck Sharp & Dohme, Mundipharma, Novartis, Pearl, Roche, and Takeda. RS, EM, DJ, and EGG are employees of AstraZeneca PLC, Barcelona, Spain. The authors report no other conflicts of interest in this work.
Databáze: MEDLINE
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