title: Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma.
abstract: BACKGROUND
  Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients.
  
  
  METHODS
  Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed.
  
  
  RESULTS
  The intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml) to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ≤ 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02).
  
  
  CONCLUSIONS
  FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.
  
  
  BACKGROUND
  Clinicaltrials.gov; NCT00766090.
authors.affiliation: School of Translational Medicine, University of Manchester, Manchester, UK. ashley.woodcock@manchester.ac.uk
authors.forename: Ashley
authors.initials: A
authors.lastname: Woodcock
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.forename: Neil G
authors.initials: NG
authors.lastname: Snowise
authors.forename: Lucy
authors.initials: L
authors.lastname: Frith
authors.forename: Loretta
authors.initials: L
authors.lastname: Jacques
authors.forename: Brett
authors.initials: B
authors.lastname: Haumann
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D015415:Biomarkers; C523187:fluticasone furoate; D006854:Hydrocortisone