Journal Article

Abediterol, a novel long-acting β2-agonist: bronchodilation, safety, tolerability and pharmacokinetic results from a single-dose, dose-ranging, active-comparator study in patients with COPD

Seoane, Beatriz, de Miquel, Gonzalo, Ruiz, Sandrine, Pujol, Helena, Jimenez, Eulalia, Astbury, Carol, Beier, Jutta, Massana, Eric

2016

Overview

Background Abediterol is a novel, once-daily long-acting β 2 -agonist in development for the treatment of chronic obstructive pulmonary disease (COPD) and asthma in combination with an anti-inflammatory agent. This Phase IIa, randomised, double-blind, crossover study investigated the bronchodilation, safety, tolerability and pharmacokinetics of abediterol in patients with moderate to severe COPD. Methods Seventy patients (aged ≥40 years, Global initiative for chronic Obstructive Lung Disease Stage II/III) were randomised (1:1:1:1:1:1) to single doses of abediterol 0.625, 2.5, 5 or 10 μg, indacaterol 150 μg or placebo. Spirometry was performed up to 36 h post-dose. Pharmacokinetics were assessed in a subset of patients ( N  = 20). Safety and tolerability were evaluated throughout the study. Results Abediterol (all doses) significantly improved change from baseline in trough forced expiratory volume in 1 s (FEV 1 ) compared with placebo (0.102, 0.203, 0.233 and 0.259 L for abediterol 0.625, 2.5, 5 and 10 μg, respectively; all p  < 0.0001; primary endpoint). Abediterol 2.5, 5 and 10 μg significantly improved trough FEV 1 compared with indacaterol 150 μg (0.092, 0.122 and 0.148 L, respectively; all p  < 0.0001). Improvements in bronchodilation were maintained at all time points post-dose versus placebo (all abediterol doses) and from 15 or 30 min post-dose versus indacaterol 150 μg with abediterol 2.5, 5 and 10 μg (all p  < 0.05). Abediterol had low systemic exposure; incidence of treatment-emergent adverse events was similar between treatment groups. Conclusions All doses of abediterol (0.625–10 μg) provided clinically and statistically significant, dose-dependent improvements in bronchodilation versus placebo, and abediterol 2.5, 5 and 10 μg gave significant improvements versus indacaterol. All doses of abediterol were safe and well tolerated in patients with COPD. Trial registration Clinicaltrials.gov NCT01425814 . Registered 29 August 2011.

• Publisher: BioMed Central,BioMed Central Ltd
• Subject: Administration, Inhalation / Adrenergic beta-2 Receptor Agonists - pharmacokinetics / Adrenergic beta-2 Receptor Agonists - therapeutic use / Adult / Aged / Anti-inflammatory drugs / Asthma / Bronchodilator agents / Bronchodilator Agents - pharmacokinetics / Bronchodilator Agents - therapeutic use / Care and treatment / Clinical trials / COPD and occupational lung disease / Critical Care Medicine / Cross-Over Studies / Dosage and administration / Dose-Response Relationship, Drug / Double-Blind Method / Female / Forced Expiratory Volume - drug effects / Germany / Humans / Indans - therapeutic use / Intensive / Internal Medicine / Male / Medicine / Medicine & Public Health / Middle Aged / Patient outcomes / Pneumology/Respiratory System / Pulmonary Disease, Chronic Obstructive - drug therapy / Quinolones - pharmacokinetics / Quinolones - therapeutic use / Research Article / Safety and security measures / Spirometry / Treatment Outcome