Effect of Nebulized Arformoterol on Airway Function in COPD: Results from Two Randomized Trials

Abstract

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 μ g BID, 25 μ g BID, 50 μ g QD) and salmeterol MDI (42 μ g 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 μ g BID: 11.4% [8.4, 14.3]; 25 μ g BID: 15.4% [12.2, 18.6]; 50 μ 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 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.

Key words: :

• long-acting β₂-agonists
• chronic obstructive pulmonary disease
• lung function
• pulmonary function testing
• placebo-controlled
• inhalation solution