Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease
Authors Ichinose M, Takizawa A, Izumoto T, Tadayasu Y, Hamilton A, Kunz C, Fukuchi Y
Received 2 April 2015
Accepted for publication 2 June 2015
Published 20 August 2015 Volume 2015:10(1) Pages 1673—1683
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Dr Richard Russell
Masakazu Ichinose,1 Ayako Takizawa,2 Toshiyasu Izumoto,2 Yusuke Tadayasu,2 Alan L Hamilton,3 Christina Kunz,4 Yoshinosuke Fukuchi5
1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany; 5Juntendo University School of Medicine, Tokyo, Japan
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 (AUC0–3), 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 AUC0–3 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 AUC0–3) supported FEV1 outcomes. All doses of olodaterol were well tolerated, and no safety concerns were identified.
Conclusion: QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.
Trial registration: ClinicalTrials.gov: NCT00824382.
Keywords: trough FEV1, trough FVC, plasma concentration, pulmonary function, once-daily, dose-finding
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