Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459

Allergy. 2014 Sep;69(9):1223-32. doi: 10.1111/all.12451. Epub 2014 Jul 14.


Background: The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. A study was conducted to determine the effect of lower once daily doses of OC000459 and to define the phenotype of subjects most responsive to treatment.

Methods: Adult subjects (percentage of predicted forced expiratory volume in 1 s (FEV1 ) 60-85%) were randomized to OC000459 at three dose levels (25 mg once daily, 200 mg once daily or 100 mg twice daily) or placebo for 12 weeks (n = 117-125 per group, full analysis set). The primary endpoint was the change from baseline in prebronchodilator FEV1 , and secondary endpoints included Asthma Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire [AQLQ(S)], and incidence of exacerbations and respiratory tract infections.

Results: OC459 caused a significant improvement in FEV1 compared with placebo at a dose of 25 mg once daily (P = 0.028). A similar increase was observed in the other dose groups, and the mean change in FEV1 in the pooled dose groups at endpoint was 95 ml greater than placebo (P = 0.024). In a post hoc analysis of atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV1 of 220 ml was observed compared with placebo (P = 0.005). The mean increase in FEV1 was more marked in younger subjects in this group: for subjects aged ≤40 years, there was a mean increase of 355 ml compared with placebo (P = 0.007). Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and the atopic eosinophilic subgroup. There was a lower incidence of exacerbations and respiratory infections in subjects treated with OC000459. There were no drug-related serious adverse events.

Conclusions: OC000459 is a safe and effective oral anti-inflammatory agent, which achieved clinically meaningful improvements in lung function and asthma control in allergic asthmatics with an eosinophil-dominant form of the disease. A dose of 25 mg given once daily was as effective as the higher doses studied.

Keywords: OC000459; asthma; eosinophil; prostaglandin D2.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anti-Asthmatic Agents / administration & dosage*
  • Asthma / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Eosinophilia / drug therapy
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Indoleacetic Acids / administration & dosage*
  • Male
  • Middle Aged
  • Quality of Life
  • Quinolines / administration & dosage*
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Young Adult


  • (5-fluoro-2-methyl-3-quinolin-2-ylmethylindo-1-yl)acetic acid
  • Anti-Asthmatic Agents
  • Indoleacetic Acids
  • Quinolines
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor