Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting β2-agonist, in patients with mild asthma

Background: Long-acting beta(2)-agonists are an established controller medication in asthma. BI 1744 is a novel L/long-acting beta(2)-agonist with a preclinical profile that suggests 24-hour bronchodilation and bronchoprotection may be achieved. Objective: To examine the bronchoprotective effects of single doses of BI 1744 against methacholine provocation in subjects with mild asthma. Methods: Thirty-one subjects with mild asthma were randomized to receive single doses of BI 1744 (2, 5, 10, 20 mu g) or placebo on separate days according to a double-blind, 5-way crossover design. Methacholine challenges were performed at 30 minutes and at 4, 8, 24, and 32 hours after each single dose of medication, and the results were expressed as PC20 FEV1. Results: All doses of BI 1744 produced statistically significant increases in the methacholine PC20 compared with placebo as long as 32 hours. The mean (geometric SEM) methacholine PC20 24 hours after dosing with placebo was 1.73 (1.13) mg/mL, which increased after 2 mu g to 3.86 (1.14) mg/mL, after 5 mu g to 5.67 (1.14) mg/mL, after 10 mu g to 9.42 (1.13) mg/mL, and after 20 mu g to 13.71 (1.14) mg/mL (all P < .0001). After 32 hours, the methacholine PC20 value remained significantly increased for all doses. No safety or tolerability concerns were identified. Conclusion: BI 1744 provides significant bronchoprotection against inhaled methacholine for up to 32 hours after single-dose administration. (J Allergy Clin Immunol 2009;124:1217-21.)