The Effect of Fluticasone furoate/umeclidinium in Adult Patients With Asthma: A Randomized, Dose-Ranging Study

Respir Med. 2015 Jan;109(1):54-62. doi: 10.1016/j.rmed.2014.09.012. Epub 2014 Oct 2.

Abstract

Background: 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.

Methods: 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 (FEV1), peak expiratory flow (PEF), and safety were assessed.

Results: Period baseline was a significant covariate, indicating a potential carryover effect between treatment periods. Across all treatment periods, trough FEV1 improved with FF/UMEC 125 and 250 versus FF (treatment difference 0.055 L [both doses]; p = 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 FEV1 with FF/UMEC 31.25, 62.5, and 250 versus FF. Trough FEV1 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.

Conclusion: 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. ClinicalTrials.gov: NCT01573624.

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

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Androstadienes / administration & dosage*
  • Androstadienes / adverse effects
  • Androstadienes / therapeutic use
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume / drug effects
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Androstadienes
  • Bronchodilator Agents
  • Drug Combinations
  • Glucocorticoids
  • Muscarinic Antagonists
  • fluticasone furoate

Associated data

  • ClinicalTrials.gov/NCT01573624