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

Abstract

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.