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

Rationale: Arformoterol, a single isomer long-acting beta(2)-agonist, was developed as an inhalation solution for the maintenance treatment of bronchoconstriction in COPD.

Methods: The pulmonary function efficacy of nebulized arformoterol (15 micro g BID, 25 micro g BID, 50 micro g QD) and salmeterol MDI (42 micro g BID) versus placebo was assessed in 1456 subjects (mean FEV(1) 1.2L, mean predicted 41%). Data were pooled from 2 identical, 12-week, double-blind, randomized trials. The percent change in trough FEV(1), percent change in FEV(1) average AUC((0 - 12 hrs)) and peak percent change FEV(1) from predose were analyzed.

Results: Improvement in trough FEV(1) averaged over 12 weeks was greater for arformoterol and salmeterol versus placebo (mean differences from placebo [95% CI] arformoterol-15 micro g BID: 11.4% [8.4, 14.3]; 25 micro g BID: 15.4% [12.2, 18.6]; 50 micro g 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 FEV(1): 13-19%; FEV(1) AUC((0 - 12 hrs)): 19-24%; peak percent change: 20-25%) and at week 12 (trough FEV(1): 10-13%; FEV(1) AUC((0 - 12 hrs)): 6-13%; peak percent change: 7-14%); all 95% CIs excluded zero. Increases in FEV(1) 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 > or = 10% increases in FEV(1) 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.