title: Once-daily dosing of levocabastine has comparable efficacy to twice-daily dosing in the treatment of allergic rhinitis assessed in an allergen challenge chamber.
abstract: OBJECTIVE
  To test the hypothesis that intranasal levocabastine (LEVO) may provide benefits as a oncedaily treatment in allergic rhinitis (AR), this non-inferiority study compared the effect at steady state of once- and twice-daily dosing with LEVO on allergen-induced nasal symptoms in AR patients.
  
  
  METHODS
  This was a randomized, double-blind, three-way cross over study evaluating the effects of repeat doses of LEVO 200 µg once-daily, LEVO 200 µg twice-daily (total dose 400 µg) and placebo, all via intranasal spray, in 78 AR patients. The primary endpoint was weighted mean total nasal symptom score (TNSS) during a 4-hour allergen exposure in the Environmental Exposure Chamber measured at trough pharmacokinetic levels either 12 (LEVO twice-daily) or 24 (LEVO once-daily) hours post-dose.
  
  
  RESULTS
  After 7 days dosing, the difference in weighted mean TNSS (0-4 hours) following LEVO once-daily versus twice-daily was 0.23 units (95% CI -0.36, 0.82), demonstrating noninferiority between the two LEVO dosing regimens by meeting the pre-specified criterion of an upper limit of 95% CI<1.0. Both dosing regimens of LEVO resulted in a statistically significant reduction in mean TNSS compared with placebo (adjusted mean difference from placebo: LEVO once-daily: -1.12 (95% CI -1.71, -0.53); LEVO twice-daily: -1.35 (-1.94, -0.76)), meeting the pre-specified criterion for superiority (upper limit of 95% CI<0). All treatments were well-tolerated.
  
  
  CONCLUSIONS
  The results of this study support the hypothesis that at steady state LEVO 200 µg taken once-daily provides similar benefit to LEVO 200 µg dosed twice-daily.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Murdoch
authors.forename: Philippe
authors.initials: P
authors.lastname: Bareille
authors.forename: Diane
authors.initials: D
authors.lastname: Ignar
authors.forename: Stephen
authors.initials: S
authors.lastname: Mark
authors.forename: Sam R
authors.initials: SR
authors.lastname: Miller
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Gupta
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Salapatek
authors.forename: Piyush
authors.initials: P
authors.lastname: Patel
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D065631:Rhinitis, Allergic / Q000188:drug therapy* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D010880:Piperidines; C047340:levocabastine