title: Abediterol (LAS100977), a novel long-acting β2-agonist: efficacy, safety and tolerability in persistent asthma.
abstract: BACKGROUND
  Abediterol (LAS100977) is a novel, long-acting β2-agonist, in development for the once-daily treatment of asthma in combination with mometasone. Here we report the results of a Phase IIa trial of single doses of abediterol added to ongoing maintenance therapy (inhaled corticosteroids) in patients with persistent mild-to-moderate asthma.
  
  
  METHODS
  This was a randomised, double-blind, placebo- and active-comparator-controlled, five-way crossover study. Male patients (18-70 years) with a clinical diagnosis of persistent asthma received abediterol (5, 10 and 25 μg), salmeterol and placebo, on top of ongoing maintenance therapy. Lung function was determined using spirometry and whole body plethysmography. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) after a single dose.
  
  
  RESULTS
  All three abediterol doses induced statistically significant increases in trough FEV1 vs placebo and salmeterol. Improvements in other lung function parameters were also statistically significantly greater with all abediterol doses vs both placebo (p < 0.0001) and salmeterol (p < 0.05) than the first assessment at 5 min post-dose. These improvements were sustained to 36 h post-dose. The profile of treatment-emergent adverse events judged as related to abediterol was consistent with that seen after adrenergic stimulation and occurred exclusively in patients who received abediterol 10 μg or 25 μg.
  
  
  CONCLUSIONS
  This first-in-patient study revealed the potent, rapid and long-acting bronchodilatory effect of abediterol in patients with persistent mild-to-moderate asthma together with an overall good safety and tolerability profile. Further studies are now underway to establish the optimal efficacy-safety-tolerability profile for this compound.
authors.affiliation: Institut für Atemwegsforchung (insaf), Villa Berg, Biebricher Allee 34, 65187 Wiesbaden, Germany. Electronic address: j.beier@insaf-wi.de.
authors.forename: J
authors.initials: J
authors.lastname: Beier
authors.affiliation: PAREXEL International GmbH, Kilinkum Westend, Haus 17, D-14050 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Fuhr
authors.affiliation: Almirall, R&D Centre, Laureà Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Massana
authors.affiliation: Almirall, R&D Centre, Laureà Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Jiménez
authors.affiliation: Almirall, R&D Centre, Laureà Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Seoane
authors.affiliation: Almirall, R&D Centre, Laureà Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: de Miquel
authors.affiliation: Almirall, R&D Centre, Laureà Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ruiz
mesh_terms: D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010993:Plethysmography, Whole Body; D015363:Quinolones / Q000008:administration & dosage / Q000627:therapeutic use*; D000068299:Salmeterol Xinafoate; D013147:Spirometry; D016896:Treatment Outcome; D055815:Young Adult
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; D015363:Quinolones; D000068299:Salmeterol Xinafoate; D000420:Albuterol
keywords: Abediterol; Asthma; Bronchodilation; LAS100977; Long-acting beta(2)-agonist; Safety