A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1 profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting ß2-agonist, in patients with chronic obstructive pulmonary disease.

ABSTRACT

BACKGROUND: 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 µg) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients received olodaterol 2 µg twice daily (BID), 5 µg BID, 5 µg once daily (QD) and 10 µg QD in a randomised sequence over 3-week treatment periods. Co-primary end points were FEV1 area 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 FEV1 versus baseline (p < 0.001) and FEV1 time profiles were nearly identical for olodaterol 5 and 10 µg QD. Olodaterol 5 µg QD demonstrated improved FEV1 AUC0-12 and similar AUC12-24 versus 2 µg BID. Olodaterol 5 µg QD showed slightly increased FEV1 AUC0-12 but lower AUC12-24 compared to 5 µg BID. Bronchodilation over 24 h was similar for olodaterol 5 µg QD and BID. All doses were well tolerated. CONCLUSIONS: Olodaterol 5 µg QD is efficacious in COPD, with a superior bronchodilatory profile compared to 2 µg 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 µg QD or 5 µg BID). TRIAL REGISTRATION ClinicalTrials.gov NCT00846768.