The 24-h FEV(1) time profile of olodaterol once daily via Respimat® and formoterol twice daily via Aerolizer® in patients with GOLD 2–4 COPD: results from two 6-week crossover studies

ABSTRACT: These studies evaluated the 24-h forced expiratory volume in 1 sec (FEV(1)) profile of once-daily (QD) olodaterol compared to placebo and twice-daily (BID) formoterol in patients with moderate to very severe chronic obstructive pulmonary disease. In two replicate, randomized, double-blind, double-dummy, four-way crossover studies, patients received olodaterol 5 and 10 μg QD, formoterol 12 μg BID, or placebo for 6 weeks in addition to usual-care background maintenance therapy. Co-primary end points were FEV(1) area under the curve from 0–12 h (AUC(0–12)) response (change from baseline) and FEV(1) AUC from 12–24 h (AUC(12–24)) response after 6 weeks, with FEV(1) AUC from 0–24 h response identified as a key secondary end point. Other secondary end points included FEV(1) AUC from 0–3 h and trough FEV(1) responses, as well as corresponding forced vital capacity responses. With both olodaterol doses, FEV(1) increased to near-maximal 30 min post-morning dose, which was sustained over 24 h. FEV(1) also increased within 30 min post-morning dose of formoterol and was sustained over 12 h; the second formoterol dose resulted in a further increase, sustained for an additional 12 h. FEV(1) AUC(0–12) and AUC(12–24) responses with both QD olodaterol doses and BID formoterol were significantly greater than placebo at 6 weeks (P < .0001). Secondary end-point outcomes were consistent with those of the co-primary end points. These data, together with those from the wider phase III clinical program, provide evidence for the 24-h bronchodilator efficacy of olodaterol QD in this patient population. TRIAL REGISTRY: ClinicalTrials.gov; NCT00931385 and NCT00932646. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-3-419) contains supplementary material, which is available to authorized users.