title: A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting β2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Olodaterol is a novel long-acting β2-agonist (LABA) with ≥24-h duration of action in preclinical and clinical studies.
  
  
  OBJECTIVE
  This Phase II, multicentre, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study evaluated four doses of once-daily olodaterol over 4 weeks in patients with chronic obstructive pulmonary disease (COPD), based on efficacy, safety and pharmacokinetic parameters.
  
  
  METHODS
  Patients received olodaterol inhalation solution or placebo via Respimat® Soft Mist™ inhaler once daily for 4 weeks. Pulmonary function testing was performed pre-dose (trough) and up to 3 or 6 h post-dose, depending on visit. Primary end point was change from baseline in trough forced expiratory volume in 1 s (FEV1) after 4 weeks' treatment. Secondary end points included change from baseline in peak FEV1 and FEV1 area under the curve from 0 to 6 h.
  
  
  RESULTS
  405 patients with COPD were randomised and assigned to treatment. Mean baseline post-bronchodilator FEV1 was 1.50 L (54% predicted). All olodaterol doses provided statistically significant increases in trough FEV1 compared to placebo (2 μg: 0.061 L [p = 0.0233]; 5 μg: 0.097 L [p = 0.0003]; 10 μg: 0.123 L [p < 0.0001]; 20 μg: 0.132 L [p < 0.0001]). A clear dose-response relationship was demonstrated regarding pulmonary function; the two highest olodaterol doses (10 and 20 μg) formed the plateau of the dose-response curve. All olodaterol doses were well tolerated, with no dose-dependent safety effects.
  
  
  CONCLUSIONS
  Once-daily olodaterol demonstrated 24-h bronchodilator efficacy, confirming its potential as a once-daily LABA for the management of COPD.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00452400.
authors.affiliation: Division of Respiratory Medicine, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: maleki.pccrc@on.aibn.com.
authors.forename: M Reza
authors.initials: MR
authors.lastname: Maleki-Yazdi
authors.affiliation: Medical Department, Institut für Gesundheitsförderung, Rüdersdorf, Brandenburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Beck
authors.affiliation: Boehringer Ingelheim (Canada) Ltd, Burlington, Ontario, Canada.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hamilton
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korducki
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Koker
authors.affiliation: Spartanburg Medical Research, Spartanburg, SC, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Fogarty
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; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D012129:Respiratory Function Tests
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; C549647:olodaterol
keywords: COPD; Long-acting β(2)-agonist; Olodaterol; Once-daily