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.

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.

Trial registration: ClinicalTrials.gov NCT01007721.

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.