Abediterol (LAS100977), a novel long-acting β2-agonist: Efficacy, safety and tolerability in persistent asthma

Background: Abediterol (LAS100977) is a novel, long-acting beta(2)-agonist, in development for the once-daily treatment of asthma in combination with mometasone. Here we report the results of a Phase I la trial of single doses of abediterol added to ongoing maintenance therapy (inhaled corticosteroids) in patients with persistent mild-to-moderate asthma. Methods: This was a randomised, double-blind, placebo- and active-comparator-controlled, five-way crossover study. Male patients (18-70 years) with a clinical diagnosis of persistent asthma received abediterol (5, 10 and 25 mu g), salmeterol and placebo, on top of ongoing maintenance therapy. Lung function was determined using spirometry and whole body plethysmography. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) after a single dose. Results: All three abediterol doses induced statistically significant increases in trough FEV1 vs placebo and salmeterol. Improvements in other lung function parameters were also statistically significantly greater with all abediterol doses vs both placebo (p < 0.0001) and salmeterol (p < 0.05) than the first assessment at 5 min post-dose. These improvements were sustained to 36 h post-dose. The profile of treatment-emergent adverse events judged as related to abediterol was consistent with that seen after adrenergic stimulation and occurred exclusively in patients who received abediterol 10 mu g or 25 mu g. Conclusions: This first-in-patient study revealed the potent, rapid and long-acting bronchodilatory effect of abediterol in patients with persistent mild-to-moderate asthma together with an overall good safety and tolerability profile. Further studies are now underway to establish the optimal efficacy safety tolerability profile for this compound. (C) 2014 Elsevier Ltd. All rights reserved.