Efficacy and safety of abediterol (LAS100977) in stable asthma: Phase II, randomized, crossover study

Background: Abediterol is a novel, once-daily LABA under development for the treatment of asthma and COPD. The peak bronchodilator effect of single doses of abediterol delivered via Genuair® vs placebo was assessed against salbutamol 400 µg in patients with persistent stable asthma. Methods: Adult patients were randomized to receive abediterol (0.313, 0.625, 1.25 or 2.5 μg), salbutamol 400 μg and placebo in a 6-period crossover study. Endpoints included change from baseline to peak (primary endpoint) and trough FEV 1 and FVC. Safety was also assessed. Results: A total of 58/62 randomized patients completed the study. Abediterol (all doses) and salbutamol achieved clinically and statistically significant improvements from baseline in peak FEV 1 vs placebo (p<0.0001; Table). Peak FEV 1 magnitude of effect with abediterol (all doses except 0.313 μg) was similar to salbutamol. Abediterol had a dose-dependent and significantly greater effect on trough FEV 1 vs placebo (p<0.0001) and vs salbutamol (p<0.0001). A similar pattern was observed for peak FVC and trough FVC. AE incidence was similar across groups. Table. Change from baseline (LS means difference vs placebo), L Abediterol, μg Salbutamol, μg 0.313 0.625 1.25 2.5 400 Peak FEV 1 0.274∗ 0.322∗ 0.371∗ 0.405∗ 0.353∗ Trough FEV 1 0.219∗ † 0.259∗ † 0.332∗ † 0.400∗ † -0.022 ∗p<0.0001 vs placebo; † p<0.0001 vs salbutamol (ANCOVA); LS, least squares Conclusions: Single doses of abediterol 0.313–2.5 μg were safe, well tolerated, and provided clinically and statistically significant improvements in peak and trough FEV 1 vs placebo. The peak bronchodilator effect of abediterol at doses ≥0.625 μg was similar to salbutamol 400 μg.