The Leading Publisher in Biotechnology

The Certihaler^™ is a new multi-dose dry powder inhaler for the delivery of formoterol (Foradil^®), a long-acting β₂-agonist. This dose-ranging study compared the efficacy and safety of formoterol 5, 10, 15 and 30 µg and placebo administered via the Certihaler or formoterol 12 µg via a single-dose dry powder inhaler (Aerolizer^®) in children with persistent asthma. This was a randomized, placebo-controlled, double-blind, double-dummy, incomplete block crossover, dose-finding and pharmacokinetic study. Children (5–12 years, n = 77) received four of the active treatments twice weekly (BID) for 1 week separated by 1-week single-blind washouts. The primary efficacy variable was 12-h AUC of FEV₁ after 1 week's treatment. Secondary variables included serial 12-h FEV₁. A subset of patients (n = 37) participated in a pharmacokinetic analysis. All formoterol doses resulted in significant increases in 12-h AUC of FEV₁ compared with placebo, and there was no difference between active treatments. The onset of action of formoterol was <3 min for all active treatments. Doses of formoterol ≥10 µg via the Certihaler increased FEV₁ significantly for up to 12 h compared with placebo. The 5 µcg dose via the Certihaler and 12 µg dose via the Aerolizer had a significant effect up to 8 and 7 h post-dose, respectively. Urinary excretion of formoterol via the Certihaler increased in a dose-proportional manner. All formoterol doses were well tolerated, but some patients experienced tremor at the 15 and 30 µg doses. Despite the lack of significant differences between the active doses in the overall bronchodilation, formoterol 10 µg BID via the Certihaler was the dose that provided the best balance between efficacy and tolerability: its duration of action was sustained over 12 h, contrary to that the lower dose (5 µg BID), whereas its tolerability, especially with regard to tremor, was better than the higher doses (15 and 30 µg BID). Overall, Certihaler 10 µg BID was not significantly different from formoterol 12 µg BID via Aerolizer.