title: A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1 profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting β2-agonist, in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  This randomised, double-blind, four-way, crossover, Phase II study compared the 24-h forced expiratory volume in 1 s (FEV1) profile of alternative dosing frequencies of two total daily doses of olodaterol (5 and 10 μg) in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Patients received olodaterol 2 μg twice daily (BID), 5 μg BID, 5 μg once daily (QD) and 10 μg QD in a randomised sequence over 3-week treatment periods. Co-primary end points were FEV1 area under the curve from 0 to 12 h (AUC0-12) and area under the curve from 12 to 24 h (AUC12-24) responses. Additional lung-function responses, pharmacokinetics and safety were assessed.
  
  
  RESULTS
  47 patients were treated. All olodaterol doses provided significant increases in FEV1 versus baseline (p < 0.001) and FEV1 time profiles were nearly identical for olodaterol 5 and 10 μg QD. Olodaterol 5 μg QD demonstrated improved FEV1 AUC0-12 and similar AUC12-24 versus 2 μg BID. Olodaterol 5 μg QD showed slightly increased FEV1 AUC0-12 but lower AUC12-24 compared to 5 μg BID. Bronchodilation over 24 h was similar for olodaterol 5 μg QD and BID. All doses were well tolerated.
  
  
  CONCLUSIONS
  Olodaterol 5 μg QD is efficacious in COPD, with a superior bronchodilatory profile compared to 2 μg BID, which is close to the same total daily dose, and a similar degree of bronchodilation over 24 h compared with double the daily dose (administered as 10 μg QD or 5 μg BID).
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00846768.
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: guy.joos@ugent.be.
authors.forename: Guy F
authors.initials: GF
authors.lastname: Joos
authors.affiliation: Longartsenpraktijk, Hasselt, Belgium.
authors.forename: Joseph-Leon
authors.initials: JL
authors.lastname: Aumann
authors.affiliation: SCS Boehringer Ingelheim Comm. V, Brussels, Belgium.
authors.forename: Carl
authors.initials: C
authors.lastname: Coeck
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korducki
authors.affiliation: Boehringer Ingelheim, Burlington, Ontario, Canada.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hamilton
authors.affiliation: Boehringer Ingelheim, Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kunz
authors.affiliation: Department of Pulmonary Disease, Martini Hospital, Groningen, The Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: Aalbers
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000368:Aged; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; C549647:olodaterol
keywords: COPD; Long-acting beta-2-agonist; Olodaterol