Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics

Clin Exp Allergy. 2014 Aug;44(8):1044-52. doi: 10.1111/cea.12357.


Background: CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses.

Objective: To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses.

Methods: In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test.

Results: Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3-10 h) ) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments.

Conclusion and clinical relevance: Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders.

Keywords: CRTH2 antagonist; allergen bronchoprovocation test; asthma; setipiprant.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Bronchial Provocation Tests
  • Exhalation
  • Forced Expiratory Volume / drug effects
  • Humans
  • Indoles / pharmacology*
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Naphthalenes / pharmacology*
  • Naphthalenes / therapeutic use*
  • Nitric Oxide / metabolism
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Respiratory Function Tests
  • Treatment Outcome
  • Young Adult


  • 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido(4,3-b)indol-5(2H)-yl)acetic acid
  • Allergens
  • Anti-Asthmatic Agents
  • Indoles
  • Naphthalenes
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Nitric Oxide
  • prostaglandin D2 receptor

Associated data

  • EudraCT/2008-001209-41