title: Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial.
abstract: BACKGROUND
  Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β(2) agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease.
  
  
  OBJECTIVE
  To determine the optimal dose(s) of FF for treating patients with asthma.
  
  
  METHODS
  An 8-week multicentre, randomised, double-blind study. 627 patients with persistent moderate-to-severe asthma, symptomatic on medium-dose inhaled corticosteroid therapy, were randomised to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a novel dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus™/Accuhaler™). The primary efficacy measure was mean change from baseline in pre-dose evening forced expiratory volume in one second (FEV(1)). Other endpoints included morning and evening peak expiratory flow, and rescue/symptom-free 24 h periods.
  
  
  RESULTS
  Each dose was significantly superior to placebo for the primary endpoint (p<0.001) with efficacy at least similar to that reported with fluticasone propionate. There was no dose-response relationship across the FF doses studied. Peak expiratory flow improved in all groups (p<0.001 vs placebo), and there were significant treatment effects on rescue/symptom-free 24 h periods with all active treatments. FF was generally well tolerated. The incidence of oral candidiasis was higher with FF 800 μg than placebo; pharmacokinetic and 24 h urinary cortisol analyses confirmed a higher systemic exposure of FF at this highest dose level.
  
  
  CONCLUSIONS
  FF doses <800 μg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 μg is an appropriate dose in patients with moderate persistent asthma. CLINICALTRIALS.GOV IDENTIFIER: NCT00603746.
authors.affiliation: Department of Medicine, University of Wisconsin, K4/910 CSC, 600 Highland Avenue, Madison, WI 53792, USA. wwb@medicine.wisc.edu
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.forename: Richard
authors.initials: R
authors.lastname: Forth
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davis
authors.forename: Loretta
authors.initials: L
authors.lastname: Jacques
authors.forename: Brett
authors.initials: B
authors.lastname: Haumann
authors.forename: Ashley
authors.initials: A
authors.lastname: Woodcock
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000730:Androstadienes; C523187:fluticasone furoate