EFFICACY AND SAFETY OF EXTRAFINE FORMOTEROL IN ASTHMATIC PATIENTS

Introduction An extrafine pMDI formulation of the long-acting beta agonist formoterol fumarate (FF) was developed, and its efficacy and safety evaluated in a controlled clinical setting. Methods A double-blind, double-dummy, single dose, randomised, 4-way crossover, placebo controlled study was conducted to evaluate efficacy and safety of FF (6 µg) one puff or two puffs versus Foradil Aerolizer (FOR) 12 µg or placebo in moderate to severe asthmatic patients. Primary endpoint was 12 hour average FEV1. Secondary efficacy endpoints were onset and duration of action. Safety endpoints were vital signs, QTc, serum potassium and glucose. Results 53 asthmatic patients (mean age 34.4 years, 32 male and 21 female) were randomized and 52 were evaluable. Average FEV1 and peak FEV1 increased significantly after FF 6 and 12 µg, with a trend toward greater efficacy with the higher FF dose. Equivalence between FF 12 µg and FOR 12 µg was demonstrated. Median time to 15% onset was 10, 15 and 10 min for FF 12 µg, FF 6 µg and FOR, respectively confirming the rapid onset of action. Median time to 15% offset was 718, 480, 719 and 240 min for FF 12 µg, FF 6 µg, FOR and Placebo respectively suggesting that FF 12 µg provides an improved coverage of the 12 hour administration interval and demonstrating a marked dose-response. No clinically significant changes were observed for blood pressure and heart rate. Serum potassium and glucose remained within normal limits for the majority of subjects. QTcB was similar for all treatments and no values exceeded 470 m/sec. There were no serious adverse events. Frequency of treatment emergent adverse events was similar in the four treatments, with tremor the most common, as expected. Conclusions This study demonstrates that extrafine FF has similar efficacy and safety as compared to FOR. FF 12 µg shows a greater and more prolonged bronchodilation compared to FF 6 µg, and confirms a marked dose–response relation for FF. This has to be considered when assessing the most appropriate therapeutic dose of FF in asthmatics.