title: The improved efficacy of a fixed-dose combination of fluticasone furoate and levocabastine relative to the individual components in the treatment of allergic rhinitis.
abstract: BACKGROUND
  Allergic rhinitis (AR) is a common chronic disease, which has significant detrimental effect on well-being and quality of life as well as substantial socio-economic impact. Combination pharmacotherapy is utilized by 40-50% of patients to treat their symptoms.
  
  
  OBJECTIVE
  To compare the effects of intranasal fluticasone furoate (FF)/levocabastine (LEVO) fixed-dose combination (FDC) with each component alone on allergen-induced nasal and ocular symptoms.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, three-way, incomplete block, cross-over, proof-of-concept study in 71 patients with AR, evaluated FF 100 μg, LEVO 200 μg and FDC (FF 100/LEVO 200 μg), once daily via intranasal spray for 8 days. On days 1 and 8, total nasal symptom score (TNSS) and total ocular symptom score (TOSS) were assessed every 15 min during a 4-h allergen exposure in the Vienna Challenge Chamber. The primary endpoint was Day 8 weighted mean TNSS.
  
  
  RESULTS
  After 8 days, FDC resulted in both statistically and clinically significant reductions in mean TNSS compared with FF and LEVO alone [adjusted mean differences (95% CI): FDC vs. FF: -2.26 (-2.90, -1.62); FDC vs. LEVO: -2.57 (-3.21, -1.93)]. All active treatments were significantly superior to placebo [adjusted mean difference (95% CI) from placebo: FDC: -4.1 (-4.86, -3.34); FF: -1.84 (-2.66, -1.03); LEVO: -1.53 (-2.34, -0.72)]. Onset of action was rapid following FDC and LEVO treatment with an approximate two unit reduction in mean TNSS from pre-dose levels by 30 min and 1 h. Mean TOSS was also reduced following all active treatments relative to placebo (range 0.6-0.8 unit reduction). All treatments were equally well tolerated.
  
  
  CONCLUSIONS
  These results suggest that once daily FF/LEVO FDC could provide a clinical therapeutic advantage to existing standard monotherapies in the treatment of moderate-to-severe AR, and support progression to evaluation in larger phase III clinical studies.
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Murdoch
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bareille
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Research Triangle Park is the official town name so no town to be entered, NC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ignar
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Miller
authors.affiliation: Quantitative Sciences India, GlaxoSmithKline, Bangalore, India.
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: R
authors.initials: R
authors.lastname: Boardley
authors.affiliation: Vienna Challenge Chamber, Allergy Centre Vienna West, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Zieglmayer
authors.affiliation: Vienna Challenge Chamber, Allergy Centre Vienna West, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Zieglmayer
authors.affiliation: Vienna Challenge Chamber, Allergy Centre Vienna West, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Lemel
authors.affiliation: Vienna Challenge Chamber, Allergy Centre Vienna West, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Horak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D065631:Rhinitis, Allergic / Q000188:drug therapy*
chemical_list: D000730:Androstadienes; D010880:Piperidines; C047340:levocabastine; C523187:fluticasone furoate
keywords: allergy; antihistamine; efficacy; steroids