title: Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis.
abstract: BACKGROUND
  The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D2 receptor chemoattractant receptor homologous molecule on T(H)2 cells (CRTH2).
  
  
  OBJECTIVE
  We sought to investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50, 200, and 400 mg twice daily), fluticasone propionate nasal spray (200 μg once daily), or oral montelukast (10 mg once daily) administered for 2 weeks in patients with SAR.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled, partial-crossover study, participants aged 18 to 65 years with a positive skin prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in the environmental challenge chamber for 6 hours. The primary efficacy variable was the total nasal symptom score assessed as the area under the curve (AUC)(0-6h).
  
  
  RESULTS
  In total, 146 patients (63.7% male; mean age, 36.1 years) were randomized. The adjusted mean total nasal symptom score AUC(0-6h) was significantly reduced versus placebo with 200 mg of BI 671800 (absolute difference, -0.85; percentage difference, -17%; P = .0026), montelukast (absolute difference, -0.74; percentage difference, -15%; P = .0115), and fluticasone propionate (absolute difference, -1.64; percentage difference, -33%; P < .0001). Compared with placebo, BI 671800 significantly reduced nasal eosinophil values (P < .05 for all doses), significantly inhibited nasal inflammatory cytokine levels (IL-4 and eotaxin, P < .05; 200 mg twice daily), and induced a dose-related reduction in ex vivo prostaglandin D2-mediated eosinophil shape change.
  
  
  CONCLUSIONS
  Two hundred milligrams of BI 671800 twice daily demonstrated efficacy in treating SAR symptoms induced by environmental challenge chamber allergen exposure and had a favorable safety profile.
authors: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany. Electronic address: norbert.krug@item.fraunhofer.de.
authors: Norbert
authors: N
authors: Krug
authors: Boehringer Ingelheim, Biberach, Germany.
authors: Abhya
authors: A
authors: Gupta
authors: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors: Philipp
authors: P
authors: Badorrek
authors: Boehringer Ingelheim, Biberach, Germany.
authors: Ruediger
authors: R
authors: Koenen
authors: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors: Meike
authors: M
authors: Mueller
authors: Boehringer Ingelheim, Biberach, Germany.
authors: Anna
authors: A
authors: Pivovarova
authors: Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn.
authors: James
authors: J
authors: Hilbert
authors: Boehringer Ingelheim, Biberach, Germany.
authors: Kristiane
authors: K
authors: Wetzel
authors: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors: Jens M
authors: JM
authors: Hohlfeld
authors: Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn.
authors: Chester
authors: C
authors: Wood
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D016207:Cytokines / Q000276:immunology; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000276:immunology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; C000605880:BI 671800; D001549:Benzamides; D016207:Cytokines; D011743:Pyrimidines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor
keywords: AE; AR; AUC; Adverse event; Allergic rhinitis; Area under the curve; BI 671800; CRTH2; Chemoattractant receptor homologous molecule on T(H)2 cells; ECC; ESC; Environmental challenge chamber; Eosinophil shape change; FP; FSC; Fluticasone propionate; Forward scatter; MMRM; Mixed-model repeated measure; PGD(2); Prostaglandin D(2); SAR; Seasonal allergic rhinitis; TNSS; Total nasal symptom score; environmental challenge chamber; inflammation; prostaglandin D(2); seasonal allergic rhinitis