Efficacy and Safety of Chemoattractant Receptor-homologous Molecule Expressed on T Helper Type 2 (CRTh2) Antagonist AZD1981 in Chronic Idiopathic Urticaria (CIU) Antihistamines

The investigators propose to use AZD1981 in subjects with chronic idiopathic urticaria (CIU) who are otherwise uncontrolled on first-line, oral antihistamine therapy. The skin lesion pathology in CIU shows a perivascular infiltrate of lymphocytes (both Th2 and Th1), eosinophils, and basophils, and closely resembles an allergen-induced late-phase reaction. Further, murine studies show that the chemoattractant receptor-homologous molecule expressed on Th2 (CRTh2) pathway is important in leukocyte recruitment following allergen challenge of the skin. Our proposed hypothesis is that AZD1981 in CIU will reduce CRTh2-expressing, leukocyte recruitment to the skin and reduce leukocyte activation through CRTh2, thus reducing the signs and symptoms in CIU refractory to control with antihistamines.

Inclusion criteria

• Females must be surgically sterile or postmenopausal or using a highly effective form of birth control throughout the duration of the study
• Females must have a negative urine pregnancy test at screening
• Must meet the criteria for Chronic Idiopathic Urticaria (CIU) as defined by itching and hives for >3 days per week for over 6 weeks with no clear cause
• CIU symptoms must have started at least 6 months prior to starting the study
• Must have moderate to severe CIU, using a standardized survey, despite taking antihistamines

Exclusion criteria

• Pregnant females or females who plan to become pregnant during the study
• Drug or alcohol abuse within the past 3 years
• Use of any investigational drug with 30 days of the start of the study
• Eczema or other skin conditions associated with itching (besides hives)
• Inability to comply with follow-up procedures
• Use of the following therapies in the past 30 days: hydroxychloroquine, sulfasalazine, dapsone, methotrexate, cyclophosphamide, Intravenous Immunoglobulin (IVIG), plasmapheresis, cyclosporine, oral or systemic steroids, or other monoclonal antibody therapies
• Use of doxepin within the past 2 weeks
• Use of either H2 antihistamines and leukotriene receptor antagonists within 7 days before starting the study (unless already on these medications for Gastroesophageal Reflux Disease (GERD), asthma or allergic rhinitis)
• Inability to take diphenhydramine (Benadryl)
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks or interfere with ability to comply with study procedures.