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

M. Reza Maleki-Yazdie， Ekkehard Beck， Alan L. Hamilton， Lawrence Korducki， Paul Koker， Charles Fogarty

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.

Conclusion

Once-daily olodaterol demonstrated 24-h bronchodilator efficacy, confirming its potential as a once-daily LABA for the management of COPD.

Trial registration: ClinicalTrials.gov: NCT00452400.

respiratory medicine

May 2015Volume 109, Issue 5, Pages 596–605

DOI: http://dx.doi.org/10.1016/j.rmed.2015.02.012 |