A Study to Investigate the Safety and Pharmacodynamics of Repeat Intranasal Administration of the TLR7 Agonist GSK2245035 in Subjects With Respiratory Allergies

Exclusion Criteria

• •History of immunological disorders or other diseases (including, but not limited to, malignancy, cardiovascular, gastro-intestinal, hepatic, renal, haematological, neurological, endocrine or pulmonary disease) that in the opinion of the investigator and GSK medical monitor may pose additional risk factors
• •Nasal conditions that according to the opinion of the investigator may affect the outcome of the study, i.e. nasal septal perforation, nasal polyps, other nasal malformations or history of frequent nosebleeds.
• •Respiratory tract infection within 4 weeks prior to the first dosing.
• •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• •A positive test for HIV antibody
• •A positive screening or pre-dose drug/alcohol screen
• •History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 14 drinks for males or greater than 7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 millileter \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• •Participation in a clinical trial with receipt of an investigational product within 3 months prior to the first dosing day.
• •Exposure to more than four new chemical entities within 6 months prior to the first dosing day.
• •History of drug or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates participation in this study.
• •Donation of blood or blood products in excess of 500 mL within a 56-day period.
• •History of sensitivity to heparin or heparin-induced thrombocytopenia
• •Unwillingness or inability to follow the procedures outlined in the protocol.
• •Subject is mentally or legally incapacitated.
• •History of severe asthma
• •Serious asthma exacerbation requiring hospital visit and/ or treatment with oral steroids or high doses of inhaled steroids within 6 weeks prior to screening
• •History of treatment with allergen-specific immunotherapy
• •Pre-bronchodilator FEV1 less than and equal to 70% of predicted at screening
• •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to first dosing, unless in the opinion of the investigator and GlaxoSmithKline (GSK) medical monitor the medication will not interfere with the study procedures or compromise subject safety. Paracetamol is an exception and will be permitted at daily doses of up to 4 g from screening to follow-up. During the dosing visits Paracetamol can be used, if needed, only if the investigator allows it.
• •Subjects using steroid treatment for allergic rhinitis and/or asthma may participate in the study if they can remain free of medication throughout the study period starting from the following periods of time prior to first dosing: Nasal steroids: 4 weeks; Oral steroids: 12 weeks; Inhaled steroids: 4 weeks
• •Subjects using other medications for their allergic rhinitis and/or asthma on an as needed basis may participate in the study if they can abstain from: Xanthines (including theophylline, but not including caffeine), anticholinergics, cromoglycates, leukotriene antagonists, 5-lipoxygenase inhibitors and longacting inhaled beta-agonists from 1 week prior to screening and throughout the study Na; Nasal antihistamines: 48 hours prior each dosing; Oral antihistamines: 76 hours prior each dosing; Nasal decongestants: 24 hours prior each dosing; Oral decongestants: 24 hours prior each dosing; Short acting inhaled beta-agonists: 48 hours prior each dosing