Efficacy, safety, and tolerability of once‐daily abediterol in patients with stable, persistent asthma: a Phase II, randomized, 7‐day, crossover study. Issue 5 (27th September 2017) - Beier, Jutta
Abstract: Abediterol is a once‐daily, long‐acting β 2 ‐adrenergic agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. We assessed the efficacy, safety, and tolerability of three dose levels of abediterol, given once daily for 7 days in patients with stable, persistent asthma. This was an ascending‐dose, three‐period incomplete crossover study design investigating three dose levels of abediterol versus placebo (EudraCT No. 2008‐003732‐38). Twenty‐eight male patients (25–59 years) were randomized to one of four treatment sequences (1:1:1:1). Follow‐up was 7 days after final treatment. Spirometry was performed regularly up to 24 h postdose Day 1, up to 36 h postdose Day 7, and at follow‐up. Vital signs, 12‐lead electrocardiogram, and clinical laboratory tests were recorded throughout. Abediterol 2.5, 5, and 10 μ g provided clinically and statistically significant improvements from baseline (predose, Day 1) in trough forced expiratory volume in 1 sec (FEV1 ) versus placebo on Day 7 (primary endpoint) of 334, 365, and 294 mL, respectively (all P < 0.01), and peak FEV1 versus placebo on Day 7 of 364 ( P < 0.001), 403 ( P < 0.001), and 375 mL ( P < 0.01), respectively. Days 1 and 7 area under the curve (AUC) parameters within each abediterol group were similar for AUC0–6, AUC0–12, AUC0–24, and AUC12–24, with dose‐dependent effects observed on Day 1. Abediterol (2.5–10 μ g) demonstrated a good safety and tolerability profile. Abediterol 2.5, 5, and 10 μ g once daily achieved statistically and clinically significant improvements in pulmonary function versus placebo over 7 days and demonstrated a safety and tolerability profile comparable with placebo.