Efficacy and safety of the long-acting β(2)-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease

BACKGROUND: Olodaterol is a novel long-acting β(2)-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 (FEV(1)) after 4 weeks of olodaterol treatment. Secondary end points included trough FEV(1) after 1 week and 2 weeks of treatment, FEV(1) area under the curve from 0 hour to 3 hours (AUC(0–3)), peak FEV(1) from 0 hour to 3 hours (peak FEV(1)), 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 FEV(1) compared to placebo at Day 29 (P<0.0001). Mean increases in peak FEV(1) and FEV(1) 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 FEV(1) 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.