Efficacy of the Oral Chemoattractant Receptor Homologous Molecule on T(H)2 Cells Antagonist Bi 671800 in Patients with Seasonal Allergic Rhinitis

Background: The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D-2 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 mu g 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, 217%; P=.0026), montelukast (absolute difference, -0.74; percentage difference, 215%; 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 D-2-mediated eosinophil shape change.Conclusion: 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.