24-hour Bronchodilation following a single dose of the novel β2-agonist olodaterol in COPD

BackgroundCurrent guidelines recommend long-acting bronchodilators as maintenance therapy in COPD when symptoms are not adequately controlled with short-acting agents. Olodaterol is a novel long-acting β2-adrenoceptor agonist with a pre-clinical profile that suggests 24-h bronchodilation may be achieved with once-daily administration.ObjectiveTo assess dose- and time-response in terms of bronchodilator efficacy, and to evaluate pharmacokinetics, safety and tolerability of single doses of olodaterol administered via Respimat® Soft Mist™ Inhaler in COPD patients.MethodsA single-center, double-blind, placebo-controlled, 5-way crossover study including 24-h spirometry (FEV1, FVC), safety, tolerability and pharmacokinetics (in a subset of patients) following dosing of olodaterol 2 μg, 5 μg, 10 μg and 20 μg; the washout period between test-days was at least 14 days. Primary endpoint of the study was the 24-h post-dosing FEV1. Patients participating in the pharmacokinetic assessments continued in an open-label extension phase to establish pharmacokinetics of olodaterol 40 μg.Results36 patients were assigned to treatment; mean baseline prebronchodilator FEV1 was 1.01 L (37% predicted normal). All doses of olodaterol provided significantly greater bronchodilation compared to placebo in 24-h FEV1 post-dose (p < 0.001); a clear dose–response relationship was observed, with values ranging from 0.070 L for olodaterol 2 μg to 0.119 L for olodaterol 20 μg. Similarly, olodaterol was superior to placebo (p < 0.001) in peak FEV1 (0.121 L to 0.213 L) and average FEV1 both during the daytime (0–12 h; ranging from 0.099 L to 0.184 L) and night-time (12–24 h; ranging from 0.074 L to 0.141 L). FVC results were consistent with those observed for FEV1. Pharmacokinetic evaluation of the peak plasma concentrations and renal excretion suggested no obvious deviation from dose-proportionality over the investigated dose range of 2 μg–40 μg; in most patients, no plasma levels could be detected following the 2 μg dose. All treatments were well tolerated with no apparent dose relation in terms of adverse events.ConclusionsOlodaterol appears to be a promising long-acting β2-adrenoceptor agonist,with bronchodilation maintained over 24 h that offers an opportunity for once-daily dosing in patients who require maintenance bronchodilator therapy for the management of COPD symptoms.

► Olodaterol is a novel once-daily β2-agonist.
► We measured bronchodilation after single doses of 2, 5, 10 and 20 μg in COPD.
► All doses of Olodaterol demonstrated dose depending bronchodilation up to 24 h.
► All doses of Olodaterol were safe and well tolerated.