Efficacy, safety, and tolerability of once‐daily abediterol in patients with stable, persistent asthma: a Phase II, randomized, 7‐day, crossover study

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 (Eudra CT 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  μg provided clinically and statistically significant improvements from baseline (predose, Day 1) in trough forced expiratory volume in 1 sec ( FEV ₁) versus placebo on Day 7 (primary endpoint) of 334, 365, and 294  mL, respectively (all P <  0.01), and peak FEV ₁ 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 AUC _0–6, AUC _0–12, AUC _0–24, and AUC _12–24, with dose‐dependent effects observed on Day 1. Abediterol (2.5–10  μg) demonstrated a good safety and tolerability profile. Abediterol 2.5, 5, and 10  μg 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.