title: Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.
  
  
  OBJECTIVE
  This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD) olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  All eligible patients were randomized to receive 2 µg, 5 µg, or 10 µg of olodaterol or placebo for 4 weeks via the Respimat Soft Mist inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1 second (FEV1) after 4 weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1 week and 2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC(0-3)), peak FEV1 from 0 hour to 3 hours (peak FEV1), and corresponding forced vital capacity (FVC) responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed.
  
  
  RESULTS
  A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P<0.0001). Mean increases in peak FEV1 and FEV1 AUC(0-3) compared to placebo were also significant (P<0.0001). A clear dose-response relationship was observed across all treatment groups. FVC responses (trough and FVC AUC(0-3)) supported FEV1 outcomes. All doses of olodaterol were well tolerated, and no safety concerns were identified.
  
  
  CONCLUSIONS
  QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00824382.
authors: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Masakazu
authors: M
authors: Ichinose
authors: Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
authors: Ayako
authors: A
authors: Takizawa
authors: Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
authors: Toshiyasu
authors: T
authors: Izumoto
authors: Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Tadayasu
authors: Boehringer Ingelheim, Burlington, Ontario, Canada.
authors: Alan L
authors: AL
authors: Hamilton
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.
authors: Christina
authors: C
authors: Kunz
authors: Juntendo University School of Medicine, Tokyo, Japan.
authors: Yoshinosuke
authors: Y
authors: Fukuchi
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000368:Aged; D019540:Area Under Curve; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007564:Japan; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; C549647:olodaterol
keywords: dose-finding; once-daily; plasma concentration; pulmonary function; trough FEV1; trough FVC