title: Dose effect of once-daily fluticasone furoate in persistent asthma: a randomized trial.
abstract: BACKGROUND
  This randomized, double-blind, multicenter study was designed to evaluate the efficacy of inhaled once-daily fluticasone furoate (FF) administered in the evening in patients with persistent asthma not controlled by short-acting beta(2) agonists, and to determine the dose(s) suitable for further development.
  
  
  METHODS
  Of 1459 patients screened, 598 received one of six treatments: placebo, FF (25 μg, 50 μg, 100 μg or 200 μg) once daily each evening, or fluticasone propionate (FP) 100 μg twice daily for 8 weeks. The primary endpoint was change from baseline in pre-dose evening forced expiratory volume in 1 s (FEV(1)).
  
  
  RESULTS
  A dose-response effect was observed for once-daily FF 25-200 μg including (p < 0.001) and excluding placebo (p = 0.03). FF 50-200 μg once daily significantly increased FEV(1) from baseline (p < 0.05 vs placebo), by >200 mL for FF 100 μg and 200 μg. Significant improvements were also achieved for peak expiratory flow, and percentage symptom-free and rescue-free 24 h periods. The magnitude of effect was at least as good as twice-daily FP. Overall, once-daily FF was well tolerated with no systemic corticosteroid effects.
  
  
  CONCLUSIONS
  FF 50-200 μg/day once daily in the evening demonstrated dose-related efficacy in asthma with 100-200 μg appearing to be the optimal doses for further evaluation. ClinicalTrials.gov: NCT00603382.
authors.affiliation: Department of Medicine, University of Cape Town, Cape Town, South Africa. Eric.Bateman@uct.ac.za
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.forename: Ashley
authors.initials: A
authors.lastname: Woodcock
authors.forename: Richard
authors.initials: R
authors.lastname: Forth
authors.forename: Hilary
authors.initials: H
authors.lastname: Medley
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: William W
authors.initials: WW
authors.lastname: Busse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D000068298:Fluticasone; C523187:fluticasone furoate