SB705498 Proof of Concept Chamber Challenge in Subjects With Non Allergic Rhinitis

Inclusion Criteria

Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

• Diagnosis of NAR, as determined by the presence of perennial rhinitis symptoms that last for several months per year, for more than 1 year and are not attributed to allergy, infections or nasal abnormalities. Positive history of rhinitis symptoms triggered by environmental provocateurs (e.g. weather changes, irritants, air pollution etc), but not allergens.
• Normal levels of total plasma IgE and negative allergy skin or Rast tests to common aeroallergens.
• Male or female between 18 and 65 years of age inclusive.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a \documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

Subjects who are using some of the medications below on an as needed basis, may participate in the study if they remain free of medication for the following periods of time prior to each visit:

• Nasal antihistamines: 48 hours
• Oral antihistamines A (cetirizine, fexofenadine, loratadine, desloratadine): 7 days
• Oral antihistamines B (all others): 7 days
• Nasal decongestants: 24 hours
• Oral decongestants: 24 hours
• Nasal glucocorticosteroids: 4 weeks
• Inhaled glucocorticoids: 4 weeks
• Oral glucocorticosteroids: 12 weeks
• Oral leukotriene receptor antagonists: 7 days
• Oral 5-lipoxygenase inhibitors: 7 days
• Oral methylxanthines: 7 days Subjects with recent upper respiratory tract infections (URTIs) will be allowed in the study only if their nasal symptoms have been completely resolved for more than 3 weeks prior to screening.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.