Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting beta sub(2-agonist, in patients with mild asthma)

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 [micro]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 PC sub(20 FEV) sub(1). Results: All doses of BI 1744 produced statistically significant increases in the methacholine PC sub(20 compared with placebo as long as 32 hours. The mean (geometric SEM) methacholine PC) sub(2)0 24 hours after dosing with placebo was 1.73 (1.13) mg/mL, which increased after 2 [micro]g to 3.86 (1.14) mg/mL, after 5 [micro]g to 5.67 (1.14) mg/mL, after 10 [micro]g to 9.42 (1.13) mg/mL, and after 20 [micro]g to 13.71 (1.14) mg/mL (all P .0001). After 32 hours, the methacholine PC sub(20 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.)