A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting [beta]2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease

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(TM) 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 FEV1and FEV1area under the curve from 0 to 6 h. Results 405 patients with COPD were randomised and assigned to treatment. Mean baseline post-bronchodilator FEV1was 1.50 L (54% predicted). All olodaterol doses provided statistically significant increases in trough FEV1compared to placebo (2 [micro]g: 0.061 L [p = 0.0233]; 5 [micro]g: 0.097 L [p = 0.0003]; 10 [micro]g: 0.123 L [p < 0.0001]; 20 [micro]g: 0.132 L [p < 0.0001]). A clear dose-response relationship was demonstrated regarding pulmonary function; the two highest olodaterol doses (10 and 20 [micro]g) 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.