title: Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies.
abstract: BACKGROUND
  Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks.
  
  
  METHODS
  A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100-1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS).
  
  
  RESULTS
  579 participants were randomized in the Phase 2 trial (mean age 41.6-43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5-40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (-0.15 [95% CI -0.29, -0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (-0.02 [95% CI -0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile.
  
  
  CONCLUSIONS
  The Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies.Trial registrationNCT01241214 and NCT01484119.
authors.affiliation: Sylvana Research Associates, 7711 Louis Pasteur Drive, Suite 406, San Antonio, TX 78229 USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Ratner
authors.affiliation: Diagnostics Research Group, San Antonio, TX USA.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Andrews
authors.affiliation: Central Texas Health Research, New Braunfels, TX USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Hampel
authors.affiliation: Southwest Allergy and Asthma Center, San Antonio, TX USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Martin
authors.affiliation: Kerrville Research Associates, Kerville, TX USA.
authors.forename: Dale E
authors.initials: DE
authors.lastname: Mohar
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Bourrelly
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Parisa
authors.initials: P
authors.lastname: Danaietash
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Mangialaio
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Abdel
authors.initials: A
authors.lastname: Hmissi
authors.affiliation: Isis Clinical Research, Austin, TX USA.
authors.forename: Jay
authors.initials: J
authors.lastname: van Bavel
keywords: Allergy; Efficacy; Mountain Cedar pollen; Rhinitis; Safety; Setipiprant