ABSTRACT
BACKGROUND: Determination of device comparability for new inhaled medications is essential. OBJECTIVE: To evaluate the methacholine bronchoprotection afforded by formoterol, 12 microg, delivered via Clickhaler and Aerolizer dry powder inhalers and a pressurized metered-dose inhaler (pMDI) in mild-to-moderate asthmatic patients. METHODS: Two separate randomized, double-blind, double-dummy, crossover studies were performed. Peak bronchoprotection (30 minutes) was measured after administration of a single dose in a placebo-controlled study (n = 16). First-dose (8 hours) and trough (12 hours) protection were evaluated after 2 weeks (n = 28). Doubling dilution differences (DDD) in the methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% from baseline were compared, with equivalence defined if the 95% confidence interval was within the predefined equivalence limits of +/- 1.5 DDD (peak) and +/- 1.0 DDD (trough). RESULTS: For peak single-dose effects, DDD (95% confidence interval) data showed significant protection vs placebo for all devices but no significant differences among active inhalers. For trough first-dose effects, there was significant protection vs baseline for all devices and equivalence for Clickhaler vs Aerolizer (-0.41; -0.85 to 0.04) and Aerolizer vs pMDI (-0.27; -0.66 to 0.13) but not for Clickhaler vs pMDI (-0.68; -1.12 to -0.23). For trough effects after 2 weeks, there was significant residual protection from baseline and equivalence for Clickhaler vs Aerolizer (-0.32; -0.94 to 0.30), Clickhaler vs pMDI (0.34; -0.96 to 0.27), and Aerolizer vs pMDI (-0.02; -0.57 to 0.52). CONCLUSIONS: Formoterol delivered by 3 different inhalers exhibited a significant degree of peak and trough bronchoprotection after single and repeated dosing, with most comparisons being within predefined equivalence limits.
