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

Abediterol is a once-daily, long-acting (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 7days 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 (25-59years) were randomized to one of four treatment sequences (1:1:1:1). Follow-up was 7days after final treatment. Spirometry was performed regularly up to 24h postdose Day 1, up to 36h postdose Day 7, and at follow-up. Vital signs, 12-lead electrocardiogram, and clinical laboratory tests were recorded throughout. Abediterol 2.5, 5, and 10g provided clinically and statistically significant improvements from baseline (predose, Day 1) in trough forced expiratory volume in 1sec (FEV1) versus placebo on Day7 (primary endpoint) of 334, 365, and 294mL, respectively (all P<0.01), and peak FEV1 versus placebo on Day7 of 364 (P<0.001), 403 (P<0.001), and 375mL (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 (2.5-10g) demonstrated a good safety and tolerability profile. Abediterol 2.5, 5, and 10g once daily achieved statistically and clinically significant improvements in pulmonary function versus placebo over 7days and demonstrated a safety and tolerability profile comparable with placebo.