Effect of nebulized arformoterol on airway function in COPD: Results from two randomized trials

Rationale: Arformoterol, a single isomer long-acting β2-agonist, was developed as an inhalation solution for the maintenance treatment of bronchoconstriction in COPD. Methods: The pulmonary function efficacy of nebulized arformoterol (15 μg BID, 25 μg BID, 50 μg QD) and salmeterol MDI (42 μg BID) versus placebo was assessed in 1456 subjects (mean FEV1 1.2L, mean predicted 41%). Data were pooled from 2 identical, 12-week, double-blind, randomized trials. The percent change in trough FEV1, percent change in FEV1 average AUC(0 - 12 hrs) and peak percent change FEV1 from predose were analyzed. Results: Improvement in trough FEV1 averaged over 12 weeks was greater for arformoterol and salmeterol versus placebo (mean differences from placebo [95% CI] arformoterol-15 μg BID: 11.4% [8.4, 14.3]; 25 μg BID: 15.4% [12.2, 18.6]; 50 μg QD: 10.9% [7.9, 13.9]); salmeterol: (11.6% [8.8, 14.4]). Greater improvements versus placebo occurred after the first dose (mean differences between arformoterol and placebo for trough FEV1: 13-19%; FEV1 AUC(0 - 12 hrs): 19-24%; peak percent change: 20-25%) and at week 12 (trough FEV1: 10-13%; FEV1 AUC(0 - 12 hrs): 6-13%; peak percent change: 7-14%); all 95% CIs excluded zero. Increases in FEV1 AUC(0 - 12 hrs) and peak percent change were greater for arformoterol than for salmeterol (95% CIs excluded zero). After 12 weeks, 78-87% of arformoterol subjects had ≥ 10% increases in FEV1 from pre-dose (56% salmeterol, 44% placebo); the median time to response was 3-13 minutes (142 minutes salmeterol). Conclusions: In these trials, COPD subjects administered nebulized arformoterol demonstrated significant and sustained improvement in lung function over 12 weeks.