title: Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy.
abstract: BACKGROUND
  Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS.
  
  
  METHODS
  This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations.
  
  
  RESULTS
  In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period.
  
  
  CONCLUSIONS
  VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed.
  
  
  BACKGROUND
  NCT01573767 (ClinicalTrials.gov).
authors.affiliation: GlaxoSmithKline, Stockley Park West, 1 - 3 Iron Bridge Road, Uxbridge, Middlesex, UB11 1BT, UK. amanda.j.oliver@gsk.com.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Oliver
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO, USA.
authors.forename: Ronina A
authors.initials: RA
authors.lastname: Covar
authors.affiliation: GlaxoSmithKline, Stockley Park West, 1 - 3 Iron Bridge Road, Uxbridge, Middlesex, UB11 1BT, UK.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Goldfrad
authors.affiliation: Southern California Clinical Trials, Newport Beach, CA, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Klein
authors.affiliation: University of Southern Denmark, Pediatric Research Unit, Kolding Hospital, Kolding, Denmark.
authors.forename: Søren E
authors.initials: SE
authors.lastname: Pedersen
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.affiliation: GlaxoSmithKline, Stockley Park West, 1 - 3 Iron Bridge Road, Uxbridge, Middlesex, UB11 1BT, UK.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Tomkins
authors.affiliation: Clinica Ricardo Palma, Javier Prado Este 1166 San Isidro, Lima, Perú
authors.forename: César
authors.initials: C
authors.lastname: Villarán
authors.affiliation: Blizard Institute, Queen Mary University London, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grigg
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy*; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D015990:Placebo Effect; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; C550468:vilanterol; D000068298:Fluticasone
keywords: Asthma; Children; Dose response; Efficacy; Fluticasone propionate; Safety; Vilanterol