The effect of fluticasone furoate/umeclidinium in adult patients with asthma: A randomized, dose-ranging study. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Lee, Laurie A.; Yang, Shuying; Kerwin, Edward; Trivedi, Roopa; Edwards, Lisa D.; Pascoe, Steven
• Is Part Of: Respiratory medicine. Volume 109:Issue 1(2015)
• Page Start: 54
• Page End: 62
• 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.2014.09.012
• 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">We evaluated the dose–response of umeclidinium (UMEC; a long-acting muscarinic antagonist) combined with fluticasone furoate (FF; an inhaled corticosteroid [ICS]) in patients with asthma.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">In a double-blind, three-period crossover study, 421 subjects (symptomatic on ICS), were randomized to a sequence of three of seven treatments: FF 100 mcg alone, FF 100 mcg combined with UMEC (15.6, 31.25, 62.5, 125, or 250 mcg), or vilanterol 25 mcg (a long-acting β-agonist), inhaled once-daily for 14 days (12–14-day washout). Trough forced expiratory volume in one second (FEV<sub>1</sub>), peak expiratory flow (PEF), and safety were assessed.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">Period baseline was a significant covariate, indicating a potential carryover effect between treatment periods. Across all treatment periods, trough FEV<sub>1</sub> improved with FF/UMEC 125 and 250 versus FF (treatment difference 0.055 L [both doses]; <italic>p</italic> = 0.018). FF/UMEC increased morning (15.9–22.9 L/min) and evening (16.2–28.8 L/min) PEF versus FF. As intended assessments were confounded, post hoc Period 1 data analyses were performed, demonstrating significant increases in trough FEV<sub>1</sub> with FF/UMEC 31.25, 62.5, and 250 versus FF. Trough FEV<sub>1</sub> improvements with FF/UMEC were greater in subjects with fixed (0.095–0.304 L) versus non-fixed (−0.084 to 0.041 L) obstruction. The incidence of on-treatment adverse events was 13–25% across groups. No treatment-related effects on laboratory parameters were reported.</p> </sec> <sec> <title id="sectitle0030">Conclusion</title> <p id="abspara0025">FF/UMEC may be a viable treatment for patients with asthma symptomatic on ICS; benefit may be most prominent in those with fixed obstruction. The carryover effect suggests future UMEC studies should use an alternative design.</p> <p id="abspara0030">ClinicalTrials.gov: <ext-link ext-link-type="unknown" id="intref0010" xlink:type="simple" xlink:href="ctgov:NCT01573624" xmlns:xlink="http://www.w3.org/1999/xlink">NCT01573624</ext-link>.</p> </sec> </abstract>