PURPOSE:The long-term safety and efficacy of two long-acting β2-agonists (LABAs) arformoterol (administered via nebulization) and racemic formoterol DPI were compared in subjects with COPD in a multi-center, 6-month randomized, double-blind, double-dummy clinical trial.
METHODS:COPD subjects (mean FEV1 1.21 L, ∼41.0 % predicted) were randomized to receive either nebulized arformoterol (15μg BID [n=149]: 25μg BID [n=147]) or formoterol (12μg BID [n=147]). The primary endpoint was frequency of adverse events (AEs). Secondary endpoints included evaluation of pulmonary function and use of rescue medication.
RESULTS:The frequency of any adverse event for arformoterol 15 μg BID, 25 μg BID and racemic formoterol DPI 12 μg BID were 67.8%, 76.2% and 66.7%, respectively. The cumulative frequency of serious adverse events (SAEs) were 13.4%, 6.8%, and 9.5%, respectively, and 6.0%, 2.7%, and 4.1% for respiratory SAEs. Study discontinuations due to an AE occurred in 10.1%, 10.9%, and 8.2% of subjects in the 3 treatment groups, respectively. COPD exacerbations occurred in 31.5%, 29.3% and 22.4% of subjects, respectively. In all groups, exacerbations occurred with less frequency after 3- to 6-months of treatment compared with the first 3-months. Following the first study dose, mean FEV1AUC0–6 improved significantly from baseline for all treatment groups (arformoterol 15μg: 19.4%, 25 μg: 23.1%, formoterol: 16.9%). This improvement was sustained at 6-months (18.8%, 22.5%, and 16.2%; respectively). The 24-hour trough FEV1 also improved significantly for all treatment groups both after first dose (arformoterol 15μg: 14.9%, 25μg: 14.4%, formoterol: 14.1%) and at 6-months (10.2%, 13.4%, and 10.1%, respectively). Similarly, peak FEV1 improved significantly from baseline post-first dose (range: 26.3% to 32.3%), increases that were sustained at 6-months (range: 25.7% to 31.6%). Use of the short acting bronchodilators ipratropium and albuterol demonstrated significant decreases of -0.8 to -1.3 actuations/day for each of the treatments and remained stable over the entire 6-months.
CONCLUSION:In this study, all LABA treatments were well-tolerated, improved pulmonary function, and reduced short-acting inhaled bronchodilator use over 6-months.
CLINICAL IMPLICATIONS:Arformoterol and formoterol are effective maintenance bronchodilators in COPD subjects.Study supported by Sepracor Inc.
DISCLOSURE:Nicola Hanania, Consultant fee, speaker bureau, advisory committee, etc. Dr. Hanania participated in an Advisory Board meeting sponsored by Sepracor Inc.; No Product/Research Disclosure Information