SESSION TITLE: Late-Breaking Abstracts
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Tuesday, October 29, 2013 at 04:30 PM - 05:30 PM
PURPOSE: Current treatment guidelines for patients with moderate or severe COPD recommend combination therapy with 2 or more long-acting bronchodilators with different mechanisms of action. Aclidinium, a long-acting muscarinic antagonist indicated for maintenance treatment of COPD-associated bronchospasm, was combined with formoterol, a long-acting β2-agonist, to assess efficacy and safety in patients with moderate to severe COPD.
METHODS: In this 24-week, double-blind, parallel-group trial, 1692 patients with stable COPD (mean [SD] prebronchodilator forced expiratory volume in 1 second [FEV1], 1.36 [0.53] L; postbronchodilator FEV1 % predicted, 53.5 [13.2]) were randomized (1:1:1:1:1) to twice-daily (BID) fixed-dose combination aclidinium 400 µg + formoterol 12 µg (FDC 400/12), aclidinium 400 µg + formoterol 6 µg (FDC 400/6), aclidinium 400 µg, formoterol 12 µg, or placebo. Coprimary endpoints were change from baseline to Week 24 in 1-h morning postdose FEV1 (each FDC vs aclidinium—contribution of formoterol) and in morning predose (trough) FEV1 (each FDC vs formoterol—contribution of aclidinium). Adverse events (AEs) were also assessed.
RESULTS: At Week 24, patients receiving FDC 400/12 and FDC 400/6 showed statistically significant improvements from baseline over aclidinium in 1-h postdose FEV1 (108 mL, and 87 mL, respectively, both p<0.001). FDC 400/12 significantly improved trough FEV1 vs formoterol by 45 mL (p=0.0102); numerical improvement of 26 mL was observed for trough FEV1 with FDC 400/6 vs formoterol. The most common AEs (>5% of patients in any treatment group) were cough (FDC 400/12, 5.1%; FDC 400/6, 3.9%; aclidinium, 2.1%; formoterol, 3.0%; placebo, 3.6%) and nasopharyngitis (FDC 400/12, 4.8%; FDC 400/6, 5.1%; aclidinium, 3.6%; formoterol, 6.6%; placebo, 3.6%). AEs leading to discontinuation were similar for FDC 400/12, FDC 400/6, and placebo (6.3%, 6.6%, and 6.3%, respectively) and for aclidinium and formoterol (4.7% and 4.2%, respectively). The percentages of patients reporting serious AEs were similar for all treatment arms (FDC 400/12, 5.7%; FDC 400/6, 5.4%; aclidinium 5.0%; formoterol, 4.5%; placebo, 3.6%).
CONCLUSIONS: Each aclidinium/formoterol fixed-dose combination improved bronchodilation compared with monotherapies and was well tolerated, with a similar safety profile to either drug alone or placebo.
CLINICAL IMPLICATIONS: Aclidinium/formoterol fixed-dose combination may be a useful treatment option for patients with COPD, providing greater bronchodilation than either monotherapy alone.
DISCLOSURE: Anthony D'Urzo: Consultant fee, speaker bureau, advisory committee, etc.: Dr. D'Urzo has received research, consulting and lecturing fees from GlaxoSmithKline, Sepracor, Schering Plough, Altana, Methapharma, AstraZeneca, ONO pharma, Merck Canada, Forest Laboratories, Novartis Canada/USA, Boehringer Ingelheim (Canada) Ltd, Pfizer Canada, SkyePharma, and KOS Pharmaceuticals. Victor Mergel: Employee: Forest Research Institute Anne Leselbaum: Employee: Almirall S.A. Cynthia Caracta: Employee: Forest Research Institute
Aclidinium bromide (Tudorzo/Pressaire, Eklira/Genuair, Breo/Ellipta) is approved for the maintenance treatment of COPD-associated bronchspasm. The fixed-dose combination of aclidinium bromide/formoterol fumarate is being developed, but not yet approved, for its commercial use for the treatment of COPD.