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DOI: 10.1055/s-0035-1544789
Lung function improvements with twice-daily aclidinium/formoterol fixed-dose combination in two 24-week studies in patients with COPD
Background: Combining bronchodilators with complementary mechanisms of action may improve lung function in patients with COPD. A fixed-dose combination (FDC) of the long-acting muscarinic antagonist aclidinium bromide and the long-acting β2 agonist formoterol fumarate is in clinical development.
Aim: To assess bronchodilation with aclidinium/formoterol FDC in patients with moderate-to-severe COPD.
Methods: In two multicentre, randomized Phase III studies (ACLIFORM and AUGMENT) patients were randomized to 24 weeks' double-blind treatment with inhaled aclidinium/formoterol FDC 400 µg/12 µg or 400 µg/6 µg, aclidinium 400 µg, formoterol 12 µg, or placebo, twice-daily. Co-primary endpoints at Week 24 were changes from baseline in 1-hr morning post-dose FEV1 vs aclidinium and morning pre-dose (trough) FEV1 vs formoterol.
Results: Mean baseline FEV1 was 1.38 L in ACLIFORM and 1.36 L in AUGMENT (54.2% and 53.5% predicted, respectively). Significant improvements in both co-primary endpoints were observed with both doses of the FDC at the first time-point assessed; these improvements were generally maintained at study end (Table). Additionally, each FDC produced clinically significant improvements in FEV1 vs placebo from as early as 5 minutes post-dose on Day 1 (range: 100 – 128 mL, both p < 0.0001).
Conclusions: Aclidinium/formoterol FDC 400/12 µg and 400/6 µg produced rapid, sustained improvements in bronchodilation compared with the monotherapies and placebo over six months in patients with COPD; the greatest improvements were seen with FDC 400/12 µg vs FDC 400/6 µg.
*p < 0.05; aACLIFORM (NCT01462942; aclidinium, n= 383; formoterol, n= 383; placebo, n = 194); bAUGMENT (NCT01437397; aclidinium, n= 337; formoterol, n= 332; placebo, n= 331); 'First time point assessed: ACLIFORM, Day 7; AUGMENT, Day 4; FDC, aclidinium/formoterol fixed-dose combination; FEV1, forced expiratory volume in 1 second; ITT, intent-to-treat; LSMD, least square mean difference; SE, standard error |
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FDC 400/12 µg |
FDC 400/6 µg |
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ACLIFORM |
AUGMENT |
ACLIFORM |
AUGMENT |
|
LSMD (SE), mL |
n = 385 a |
n = 335 b |
n = 381 a |
n = 333 b |
1-hr morning post-dose FEV1 vs aclidinium |
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Day 1 |
45 (11)* |
42 (11)* |
26 (11)* |
30 (11)* |
Week 24 |
125 (18)* |
108 (18)* |
69 (18)* |
87 (18)* |
1-hr morning post-dose FEV1 vs placebo |
||||
Day 1 |
210 (14)* |
205 (11)* |
191 (14)* |
193 (11)* |
Week 24 |
299 (22)* |
284 (19)* |
244 (22)* |
263 (18)* |
Morning pre-dose (trough) FEV1 vs formoterol |
||||
Week lc |
64 (13)* |
55 (12)* |
52 (13)* |
48 (12)* |
Week 24 |
85 (17)* |
45 (17)* |
53 (17)* |
26 (17) |
Morning pre-dose (trough) FEV1 vs placebo |
||||
Week lc |
147 (16)* |
152 (12)* |
134 (16)* |
145 (12)* |
Week 24 |
143 (21)* |
130 (18)* |
111 (21)* |
111 (18)* |
Funding: This study was supported by Almirall S.A., Barcelona, Spain and Forest Laboratories LLC, a subsidiary of Actavis plc, New York, NY, USA