title: Efficacy and optimal dosing interval of the long-acting beta₂ agonist, vilanterol, in persistent asthma: a randomised trial.
abstract: BACKGROUND
  Vilanterol (VI) is a novel once-daily long-acting beta₂ agonist with inherent 24-h activity. The aim of this study was to evaluate the efficacy of three once-daily doses and one twice-daily dose of VI used concurrently with ICS in adult patients (≥18 years) with persistent asthma. Safety was also assessed.
  
  
  METHODS
  Multicentre, randomised, double-blind, placebo-controlled, five-period crossover study consisting of 7-day treatment periods separated by 7-day wash-out periods. Seventy-five patients, maintained on ICS, received VI 6.25, 12.5 and 25 mcg once-daily (evening), VI 6.25 mcg twice-daily (morning/evening), and placebo. The primary endpoint was trough forced expiratory volume in 1 s (FEV(1)) (mean of 23 h and 24 h post evening dose) on Day 7; secondary endpoint was weighted mean 24-h serial FEV(1) on Day 7.
  
  
  RESULTS
  All VI groups demonstrated statistically significant increases in trough FEV(1) versus placebo (p < 0.001). There was a statistically significant increase in weighted mean 24-h FEV(1) for each VI group versus placebo (p < 0.001). The effects of once-daily VI on trough FEV(1) and weighted mean 24-h FEV(1) were dose dependent. The incidence of adverse events (AEs) was low in each VI treatment group and was not dose dependent (5-9%; placebo = 18%); no drug-related AEs or serious AEs were reported.
  
  
  CONCLUSIONS
  Once-daily treatment with VI was well tolerated and associated with improvements in lung function. The VI 6.25 mcg twice-daily dose showed the greatest change in trough FEV(1), however, similar changes in weighted mean 24-h FEV(1) with VI 12.5 mcg once-daily were observed. Although our study was not powered to demonstrate non-inferiority of once- versus twice-daily dosing of VI, the data suggest no advantage over a 24-h period of twice-daily over once-daily dosing for the same total daily dose. ClinicalTrials.gov: NCT00980200.
authors.affiliation: Carolina Research, Respiratory Medicine, Orangeburg, SC 29118-2040, USA. sterlingent531@yahoo.com
authors.forename: Richard
authors.initials: R
authors.lastname: Sterling
authors.forename: Jessica
authors.initials: J
authors.lastname: Lim
authors.forename: Lucy
authors.initials: L
authors.lastname: Frith
authors.forename: Neil G
authors.initials: NG
authors.lastname: Snowise
authors.forename: Loretta
authors.initials: L
authors.lastname: Jacques
authors.forename: Brett
authors.initials: B
authors.lastname: Haumann
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D005938:Glucocorticoids; C550468:vilanterol