A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting [beta]2-agonist, in patients with chronic obstructive pulmonary disease

This randomised, double-blind, four-way, crossover, Phase II study compared the 24-h forced expiratory volume in 1 s (FEV1) profile of alternative dosing frequencies of two total daily doses of olodaterol (5 and 10 [micro]g) in patients with chronic obstructive pulmonary disease (COPD). Methods Patients received olodaterol 2 [micro]g twice daily (BID), 5 [micro]g BID, 5 [micro]g once daily (QD) and 10 [micro]g QD in a randomised sequence over 3-week treatment periods. Co-primary end points were FEV1area under the curve from 0 to 12 h (AUC0-12) and area under the curve from 12 to 24 h (AUC12-24) responses. Additional lung-function responses, pharmacokinetics and safety were assessed. Results 47 patients were treated. All olodaterol doses provided significant increases in FEV1versus baseline (p < 0.001) and FEV1time profiles were nearly identical for olodaterol 5 and 10 [micro]g QD. Olodaterol 5 [micro]g QD demonstrated improved FEV1AUC0-12and similar AUC12-24versus 2 [micro]g BID. Olodaterol 5 [micro]g QD showed slightly increased FEV1AUC0-12but lower AUC12-24compared to 5 [micro]g BID. Bronchodilation over 24 h was similar for olodaterol 5 [micro]g QD and BID. All doses were well tolerated. Conclusions Olodaterol 5 [micro]g QD is efficacious in COPD, with a superior bronchodilatory profile compared to 2 [micro]g BID, which is close to the same total daily dose, and a similar degree of bronchodilation over 24 h compared with double the daily dose (administered as 10 [micro]g QD or 5 [micro]g BID). Trial registration ClinicalTrials.gov:NCT00846768.