title: A randomized study of BI 671800, a CRTH2 antagonist, as add-on therapy in poorly controlled asthma.
abstract: BACKGROUND
  Asthma is characterized by a complex interaction of inflammatory mediators. The prostaglandin D2 receptor, chemoattractant receptor-homologous molecule on Th2 cells (CRTH2), plays a pivotal role in the pathogenesis of allergic airway inflammation.
  
  
  OBJECTIVE
  To ealuate the efficacy, safety, and pharmacokinetics of BI 671800, a CRTH2 antagonist, when added to inhaled corticosteroid therapy in adult patients with symptomatic asthma.
  
  
  METHODS
  In this phase IIa, 12-week, randomized, double-blind, three-period, four-treatment, incomplete block crossover trial, BI 671800 was administered either as a single 400-mg dose in the morning (A.M.) or evening (P.M.), or 200 mg twice daily (A.M. and P.M.) versus placebo, together with fluticasone propionate (44 μg, two inhalations twice daily). The primary end point was the change from baseline in trough forced expiratory volume in 1 second percentage predicted after 4 weeks. The secondary end point was the change in Asthma Control Questionnaire score from baseline.
  
  
  RESULTS
  A total of 108 patients were randomized and treated. After 4 weeks, the adjusted mean (± SE) treatment differences for the primary end point versus placebo were 0.08 ± 0.62%, 0.28 ± 0.61%, and 0.67 ± 0.63% for BI 671800 at 200 mg twice daily, 400 mg A.M., and 400 mg P.M., respectively (not statistically significant). No statistically significant or clinically meaningful differences in the Asthma Control Questionnaire score were observed versus placebo. Each treatment was well tolerated.
  
  
  CONCLUSIONS
  BI 671800 at a dose of 400 mg administered for 4 weeks with fluticasone propionate did not provide clinical improvement in patients with asthma; reasons for this are unclear, but it may be due to insufficient inhibition of the CRTH2 receptor at the doses used.
authors.forename: David
authors.initials: D
authors.lastname: Miller
authors.forename: Chester
authors.initials: C
authors.lastname: Wood
authors.forename: Eric
authors.initials: E
authors.lastname: Bateman
authors.forename: Craig
authors.initials: C
authors.lastname: LaForce
authors.forename: Jon
authors.initials: J
authors.lastname: Blatchford
authors.forename: James
authors.initials: J
authors.lastname: Hilbert
authors.forename: Abhya
authors.initials: A
authors.lastname: Gupta
authors.forename: Andrew
authors.initials: A
authors.lastname: Fowler
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001549:Benzamides / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; C000605880:BI 671800; D001549:Benzamides; D011743:Pyrimidines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000068298:Fluticasone; C036293:prostaglandin D2 receptor