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 microg, AB 400 microg, or FF 12 microg, or once-daily TIO 18 microg. Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF). Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective. Normalized area under the curve (AUC)0-3/3 h FEV1 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 FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P<0.0001). AB/FF significantly improved trough FEV1 vs FF (55 mL, P<0.001) and AB was non-inferior to TIO. AB/FF significantly improved AUC0-3/3 h FEV1 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 AUC12-24/12 h vs all comparators, and in AUC0-24/24 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.
- Sethi, S.
- Kerwin, E.
- Watz, H.
- Ferguson, G. T.
- Mroz, R. M.
- Segarra, R.
- Molins, E.
- Jarreta, D.
- Garcia Gil, E.
Keywords
- Adrenergic beta-2 Receptor Agonists/*administration & dosage/adverse effects
- Aged
- Bronchodilator Agents/*administration & dosage/adverse effects
- Double-Blind Method
- Drug Combinations
- Europe
- Female
- Forced Expiratory Volume
- Formoterol Fumarate/*administration & dosage/adverse effects
- Humans
- Israel
- Lung/*drug effects/physiopathology
- Male
- Middle Aged
- Muscarinic Antagonists/*administration & dosage/adverse effects
- Pulmonary Disease, Chronic Obstructive/diagnosis/*drug therapy/physiopathology
- Recovery of Function
- Severity of Illness Index
- Time Factors
- Tiotropium Bromide/*administration & dosage/adverse effects
- Treatment Outcome
- Tropanes/*administration & dosage/adverse effects
- United States
- Vital Capacity
- *24-hour lung function
- *laba
- *lama
- *aclidinium bromide
- *bronchodilators
- 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.
