Pneumologie 2015; 69 - P347
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

D Singh 1, A D'Urzo 2, PW Jones 3, C Serra 4, V Mergel 5, A Leselbaum 4
  • 1Medicines Evaluation Unit Ltd, University of Manchester
  • 2University of Toronto
  • 3Division of Clinical Sciences, St George's, University of London
  • 4Almirall R&D Centre Barcelona
  • 5Forest Research Institute, a subsidiary of Actavis plc, New Jersey

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.

Tab. 1: Improvements in bronchodilation with aclidinium/formoterol FDCs (ACLIFORM and AUGMENT studies; ITT population)

*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

FDC 400/12 µg

FDC 400/6 µg

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

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