title: Fluticasone furoate-vilanterol 100-25 mcg compared with fluticasone furoate 100 mcg in asthma: a randomized trial.
abstract: BACKGROUND
  The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2-agonist vilanterol (VI) is under development for the treatment of asthma and chronic obstructive pulmonary disease.
  
  
  OBJECTIVE
  To compare the efficacy and safety of FF-VI and FF in patients (≥ 12 years old) with persistent asthma.
  
  
  METHODS
  In a randomized, double-blind, parallel-group study, patients (n = 609) (intent-to-treat population) received FF-VI 100-25 mcg, FF 100 mcg, or placebo once daily (evening) by using a dry powder inhaler for 12 weeks. Coprimary end points were change from baseline in trough FEV1 and serial (0-24 hours) weighted mean FEV1 (wmFEV(1)). Rescue-free 24-hour periods and safety also were assessed.
  
  
  RESULTS
  Placebo increased trough FEV1 (196 mL) and wmFEV(1) (212 mL) versus baseline. Compared with placebo, FF-VI and FF significantly improved trough FEV1 (172 mL [P < .001] and 136 mL [P = .002]), respectively, and serial wmFEV(1) (302 mL [P < .001] and 186 mL [P = .003]), respectively. Treatment differences between FF-VI and FF approached significance for serial wmFEV(1) (116 mL; P = .060) but not for trough FEV1 (36 mL; P = .405). The percentage of rescue-free 24-hour periods with FF-VI was 10.6% greater than FF and 19.3% greater than placebo. Statistically significant (P = .032) urinary cortisol suppression was observed with FF-VI (ratio, 0.82) relative to placebo, but not with FF. Adverse event and safety profiles were similar across treatment groups.
  
  
  CONCLUSIONS
  Significant improvement in lung function was observed with FF-VI and FF versus placebo in patients with persistent asthma. Improvement of FEV1 when VI was added to FF was not significant. The high placebo response in evening trough FEV1 may have influenced the assessment of efficacy.
authors.affiliation: Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem, NC. Electronic address: ebleeck@wakehealth.edu.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.affiliation: Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.affiliation: Michael G DeGroote School of Medicine, Hamilton, Ontario, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
authors.forename: Ashley
authors.initials: A
authors.lastname: Woodcock
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wis.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Clinical Research Institute of Southern Oregon, PC, Ore.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.affiliation: Quantitative Sciences Division, GlaxoSmithKline, RTP, NC.
authors.forename: Richard
authors.initials: R
authors.lastname: Forth
authors.affiliation: Respiratory Medicines Development Centre, GlaxoSmithKline, London, United Kingdom.
authors.forename: Hilary V
authors.initials: HV
authors.lastname: Medley
authors.affiliation: Respiratory Medicines Development Centre, GlaxoSmithKline, London, United Kingdom.
authors.forename: Carol
authors.initials: C
authors.lastname: Nunn
authors.affiliation: Respiratory Medicines Development Centre, GlaxoSmithKline, London, United Kingdom.
authors.forename: Loretta
authors.initials: L
authors.lastname: Jacques
authors.affiliation: Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001592:Benzyl Alcohols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002722:Chlorobenzenes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; C550468:vilanterol; C523187:fluticasone furoate
keywords: Asthma; Efficacy; Fluticasone furoate; Randomized trial; Safety; Tolerability; Vilanterol