Clinically Equivalent Bronchodilatation Achieved with Formoterol Delivered via Easyhaler® and Aerolizer®

Abstract

Background: User-friendly devices for the delivery of asthma drugs are needed to enhance treatment compliance. Formoterol inhalation powder has been developed to Easyhaler^® multidose powder inhaler to enable the treatment of all asthma severities with the same device. Objectives: This double-blind, double-dummy, single- dose, placebo-controlled, cross-over study aimed to demonstrate the non-inferiority of the bronchodilating effect of formoterol 12 µg delivered via Easyhaler versus via Aerolizer^®. In addition, dose responses following placebo, 12-µg and 48-µg doses of formoterol via Easyhaler were compared. Furthermore, onset and duration of action, and safety of formoterol inhaled using the two inhalers were compared. Methods: Sixty-seven adult asthmatic subjects showing ≧15% increase in forced expiratory volume in 1 s (FEV₁) after short-acting sympathomimetic inhalation were enrolled and completed the study. The study comprised screening and 4 treatment days, with each subject inhaling a single 12-µg dose of formoterol via Easyhaler, a 12-µg dose via Aerolizer, a 48-µg dose via Easyhaler or placebo. Repeat spirometry and vital sign measurements were performed for 12 h during treatment days. The primary efficacy variable was the area under the flow volume curve (AUC_0–12) of FEV₁. Secondary efficacy variables comprised maximum FEV₁(FEV_1max), forced vital capacity (FVC), and the need of rescue medication during the treatment days. Safety was evaluated by determining blood pressure, heart rate and the number of adverse events (AEs). Results: Results showed the non-inferiority of the bronchodilating effect of 12 µg formoterol via Easyhaler^® compared to Aerolizer^®. The Easyhaler-Aerolizer ratio for AUC_0–12 of FEV₁was 0.991 (95% confidence interval from 0.969 to 1.013). No statistically significant differences emerged for secondary efficacy variables. A statistically significant dose response was seen following placebo, 12- and 48-µg doses in FEV₁. No safety differences emerged for the 12-µg dose inhaled via Easyhaler or Aerolizer, but the incidence of AEs was higher following formoterol 48 µg and placebo treatments. Conclusions: Formoterol delivered via Easyhaler was therapeutically equivalent to Aerolizerat the 12-µg dose. The 48-µg dose via Easyhaler demonstrated statistically significantly greater bronchodilation but showed an increased occurrence of AEs.