A randomized, three-period crossover study of umeclidinium as monotherapy in adult patients with asthma

Abstract

Background: To our knowledge, no studies in patients with asthma have assessed a long-acting muscarinic antagonist in the absence of inhaled corticosteroids (ICS).

Objective: Evaluate the dose-response, efficacy, and safety of umeclidinium (UMEC) in patients with asthma not receiving ICS.

Methods: In this double-blind, three-period crossover study, 350 subjects were randomized to a sequence of three of eight inhaled treatments: UMEC 15.6, 31.25, 62.5, 125, or 250 mcg once daily (OD), UMEC 15.6 or 31.25 mcg twice daily (BID), or placebo, administered for 14 days (12-14-day washout). Trough forced expiratory volume in one second (FEV1), 0-24-h weighted mean (WM) FEV1, and safety were assessed. Serial spirometry and pharmacokinetic assessments were performed in a subgroup.

Results: Subjects had a mean baseline pre- and post-bronchodilator FEV1 of 71% and 88% predicted, respectively. Significant improvements in change from baseline trough FEV1 were observed for UMEC 15.6 OD (0.066 L; p = 0.036) and UMEC 125 OD (0.088 L; p = 0.005) versus placebo, but not other OD or BID doses. UMEC increased 0-24-h WM FEV1 versus placebo (0.068-0.121 L [p ≤ 0.017] with no clear dose-response). Treatment differences were similar for corresponding OD and BID doses in serial assessments. UMEC was rapidly absorbed, with evidence of some accumulation. The incidence of on-treatment adverse events was 9-21% for UMEC and 12% for placebo. There were no treatment-related effects on laboratory parameters.

Conclusion: The modest trough FEV1 improvements did not conclusively support a therapeutic benefit of UMEC in non-ICS treated patients with asthma.

Clinicaltrialsgov: NCT01641692.

Keywords: Asthma; Fixed-dose combination; Inhaled corticosteroid; Muscarinic antagonist; Trough FEV(1).