title: 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.
abstract: Abediterol is a novel, once-daily long-acting β2-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.
  
  
  
  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.
  
  
  
  Abediterol (all doses) significantly improved change from baseline in trough forced expiratory volume in 1 s (FEV1) 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 FEV1 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.
  
  
  
  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.
  
  
  
  Clinicaltrials.gov NCT01425814 . Registered 29 August 2011.
authors.affiliation: insaf Respiratory Research Institute, Biebricher Allee 34, 65187, Wiesbaden, Germany. j.beier@insaf-wi.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Beier
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Pujol
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Seoane
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Jimenez
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Carol
authors.initials: C
authors.lastname: Astbury
authors.affiliation: Almirall R&D Centre, Barcelona, Spain.
authors.forename: Eric
authors.initials: E
authors.lastname: Massana
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ruiz
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de Miquel
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005858:Germany; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013147:Spirometry; D016896:Treatment Outcome
chemical_list: C576952:5-(2-((6-(2,2-difluoro-2-phenylethoxy)hexyl)amino)-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; C510790:indacaterol
keywords: Bronchodilation; COPD; Chronic respiratory disease; LABA