title: The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial.
abstract: BACKGROUND
  CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D(2). The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. The objective of the present study was to determine the involvement of CRTH2 in promoting nasal and ocular symptoms in allergic subjects exposed to grass pollen.
  
  
  METHODS
  A single centre, randomised, double-blind, placebo-controlled, two-way crossover study was conducted in 35 male subjects allergic to grass pollen comparing OC000459 200 mg bid with placebo for 8 days. Subjects were exposed to grass pollen (≥ 1400 grains/m(3)) for 6 h on the 2nd and 8th days of treatment and assessed for nasal symptoms, ocular symptoms, other symptoms, nasal secretion weight and rhinomanometry over the 6-h period. After a washout period of 3 weeks, subjects were switched to the alternative treatment for a further 8 days. The trial was registered on the clinical trials.gov database (Identifier NCT01448902).
  
  
  RESULTS
  During the first treatment period, treatment with OC000459 significantly reduced both nasal and ocular symptoms in allergic subjects compared with placebo after challenge with grass pollen. A significant effect was observed on the 2nd day of dosing which was increased on the 8th day of dosing. The therapeutic effects of OC000459 persisted into the second treatment period despite a 3-week washout phase. The safety profile of OC000459 was similar to that of placebo.
  
  
  CONCLUSIONS
  Treatment with OC000459 was well tolerated and led to a significant and persistent reduction in the symptoms of rhinoconjunctivitis.
authors.affiliation: Vienna Challenge Chamber, Allergy Centre Vienna West, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Horak
authors.forename: P
authors.initials: P
authors.lastname: Zieglmayer
authors.forename: R
authors.initials: R
authors.lastname: Zieglmayer
authors.forename: P
authors.initials: P
authors.lastname: Lemell
authors.forename: L P
authors.initials: LP
authors.lastname: Collins
authors.forename: M G
authors.initials: MG
authors.lastname: Hunter
authors.forename: J
authors.initials: J
authors.lastname: Steiner
authors.forename: T
authors.initials: T
authors.lastname: Lewis
authors.forename: M A
authors.initials: MA
authors.lastname: Payton
authors.forename: C M
authors.initials: CM
authors.lastname: Perkins
authors.forename: R
authors.initials: R
authors.lastname: Pettipher
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology*; D007210:Indoleacetic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C571151:(5-fluoro-2-methyl-3-quinolin-2-ylmethylindo-1-yl)acetic acid; D000485:Allergens; D007210:Indoleacetic Acids; D011804:Quinolines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor