A randomized, three-period crossover study of umeclidinium as monotherapy in adult patients with asthma. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Lee, Laurie A.; Briggs, Anne; Edwards, Lisa D.; Yang, Shuying; Pascoe, Steven
• Is Part Of: Respiratory medicine. Volume 109:Issue 1(2015)
• Page Start: 63
• Page End: 73
• Publication Date: 2015-01
• Subjects: Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2014.10.009
• Languages: English
• ISSNs: 0954-6111

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Summary</title> <sec> <title id="sectitle0015">Background</title> <p id="abspara0010">To our knowledge, no studies in patients with asthma have assessed a long-acting muscarinic antagonist in the absence of inhaled corticosteroids (ICS).</p> </sec> <sec> <title id="sectitle0020">Objective</title> <p id="abspara0015">Evaluate the dose–response, efficacy, and safety of umeclidinium (UMEC) in patients with asthma not receiving ICS.</p> </sec> <sec> <title id="sectitle0025">Methods</title> <p id="abspara0020">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 (FEV<sub>1</sub>), 0–24-h weighted mean (WM) FEV<sub>1</sub>, and safety were assessed. Serial spirometry and pharmacokinetic assessments were performed in a subgroup.</p> </sec> <sec> <title id="sectitle0030">Results</title> <p id="abspara0025">Subjects had a mean baseline pre- and post-bronchodilator FEV<sub>1</sub> of 71% and 88% predicted, respectively. Significant improvements in change from baseline trough FEV<sub>1</sub> were observed for UMEC 15.6 OD (0.066 L; <italic>p</italic> = 0.036) and UMEC 125 OD (0.088 L; <italic>p</italic> = 0.005) versus placebo, but not other OD or BID doses. UMEC increased 0–24-h WM FEV<sub>1</sub> versus placebo (0.068–0.121 L [<italic>p</italic> ≤ 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.</p> </sec> <sec> <title id="sectitle0035">Conclusion</title> <p id="abspara0030">The modest trough FEV<sub>1</sub> improvements did not conclusively support a therapeutic benefit of UMEC in non-ICS treated patients with asthma.</p> </sec> <sec> <title id="sectitle0040">ClinicalTrials.gov</title> <p id="abspara0035"> <ext-link ext-link-type="unknown" id="intref0010" xlink:type="simple" xlink:href="ctgov:NCT01641692" xmlns:xlink="http://www.w3.org/1999/xlink">NCT01641692</ext-link>.</p> </sec> </abstract>