A Pilot Study In Adults And Adolescents With Irritant (Non-Allergic) Rhinitis

Inclusion Criteria:

• Informed consent: Subject is willing and able to provide consent to participate in thestudy. For subjects who are under 18 years of age, an appropriately signed and datedassent must be obtained from the parents or guardian.

• Outpatient: Subject is treatable on an outpatient basis.

• Age: 12 years of age or older at Visit 2.

• Gender: Male or eligible female To be eligible for entry into the study, females of childbearing potential must commit tothe consistent and correct use of an acceptable method of birth control, as defined by thefollowing:

• Male partner who is sterile prior to the female subject's entry into the study and isthe sole sexual partner for that female subject

• Implants of levonorgestrel

• Injectable progestogen

• Oral contraceptive (either combined estrogen/progestin or progestin only)

• Any intrauterine device (IUD) with a documented failure rate of less than 1% per year,or

• Females of childbearing potential who are not sexually active must commit to completeabstinence from intercourse for two weeks before exposure to the study drug,throughout the clinical trial, and for a period after the trial to account forelimination of the drug (minimum of six days).

• Double barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus amale condom or a spermicide and female diaphragm). Female subjects should not be enrolled if they plan to become pregnant during the time ofstudy participation. A urine pregnancy test will be performed at the screening visit (Visit 1), the randomisation visit (Visit 2) and at the final visit (Visit 6 or Early Withdrawal).

• Clinical history: Diagnosis or evidence of air pollution triggers as the predominantirritant trigger for their rhinitis symptoms to include ALL of the following:

• A two year clinical history of irritant (non-allergic) rhinitis triggeredpredominantly by air pollution exposure (written or verbal confirmation) in theopinion of the investigator and evidence of symptoms such as rhinorrhea, nasalcongestion and postnasal drip relating to concentration of air particulates, airquality and levels of exposure.

• Based on the trigger questionnaire, subjects must indicate that air pollution isthe predominant trigger that makes their rhinitis symptoms worse completed atVisit 1.

• Negative skin test (by prick method) response to seasonal allergens (includingtree, grass and weed pollens) and perennial allergens (including animal dander,house dust mites, cockroach and mould) relevant to the geographical areacompleted at Visit 1. A negative response for allergen skin prick testing is defined as a wheal <3 mm than thediluent control.

• Positive response to a histamine skin test (prick method) completed at Visit 1. Apositive response for histamine skin prick testing is defined as a wheal ≥3 mm largerthan the diluent control.

• Normal sinus radiograph (Waters view) to rule out sinusitis (presence of mucosalthickening of ≥6 mm at the point of maximal thickening or an air fluid level oropacification). The sinus radiograph will be scheduled at Visit 1.

• Ability to comply with study procedures: Subject understands and is willing, ableand likely to comply with study procedures and restrictions.

• Literate: Subject must be able to read, comprehend, and record information inEnglish or native language. Randomization Criteria

• Average of the last 8, reflective, total nasal symptom score (rTNSS) assessments (4morning [AM] assessments, 4 evening [PM] assessments) over the four 24-hour periodsprior to randomisation must be greater than/equal to 4.5.

• Average of the last 8 reflective nasal symptom assessments for congestion (4 AMassessments, 4 PM assessments) over the four 24-hour periods prior to randomisationmust be greater than/equal to 2.

• A subject must have completed 80% of assessments on the screening symptom diary card.

Exclusion Criteria:

• Significant concomitant medical conditions, defined as but not limited to:

• a historical or current evidence of clinically significant uncontrolled diseaseof any body system (e.g., tuberculosis, psychological disorders, eczema).Significant is defined as any disease that, in the opinion of the investigator,would put the safety of the subject at risk through study participation or whichwould confound the interpretation of the study results if the disease/conditionexacerbated during the study.

• a severe physical obstruction of the nose (e.g., deviated septum or nasal polyp)or nasal septal perforation that could affect the deposition of double blindintranasal study drug

• nasal (e.g., nasal septum) or ocular injury/surgery in the last 3 months

• asthma, with the exception of mild intermittent asthma [Global Initiative forAsthma (GINA), 2006]. NOTE: Subjects will be allowed to use short-acting inhaledbeta2 agonists ONLY on an as needed basis.

• rhinitis medicamentosa

• bacterial or viral infection (e.g., common cold) of the upper respiratory tractwithin two weeks of Visit 1 or during the screening period

• documented evidence of acute or significant chronic sinusitis, as determined by asinus radiograph (Waters view) done at Visit 1

• current or history of glaucoma and/or current cataract or ocular herpes simplex

• physical impairment that would affect the subject's ability to participate in thestudy

• clinical evidence of a Candida infection of the nose or oropharynx

• history of psychiatric disease, intellectual deficiency, poor motivation,substance abuse (including drug and alcohol) or other conditions that will limitthe validity of informed consent or that would confound the interpretation of thestudy results

• history of or current use of cocaine

• history of adrenal insufficiency

• Chickenpox or measles within 3 weeks of Visit 1. A subject is not eligible ifhe/she currently has chickenpox or measles, or has been exposed to chickenpox ormeasles during the last 3 weeks and is non-immune. If a subject developschickenpox or measles during the study, he/she will be withdrawn from the study.If a non-immune subject is exposed to chickenpox or measles during the study,his/her continuation in the study will be at the discretion of the investigator,taking into consideration the likelihood of developing active disease.

• Use of corticosteroids, defined as:

• Intranasal corticosteroid within 4 weeks prior to Visit 1.

• Inhaled, oral, intramuscular, intravenous, ocular, and/or dermatologicalcorticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less,or equivalent) within 8 weeks prior to Visit 1.

• Use of other allergy medications within the timeframe indicated relative to Visit 1

• Intranasal or ocular cromolyn within 14 days prior to Visit 1

• Short-acting prescription and over the counter (OTC) antihistamines, includingocular preparations and antihistamines contained in insomnia and 'nighttime' painformulations taken for insomnia, within 7 days prior to Visit 1

• Long-acting antihistamines within 10 days prior to Visit 1: loratadine,desloratadine, fexofenadine, cetirizine

• Long-acting antihistamine, astemizole, within 12 weeks prior to Visit 1

• Intranasal antihistamines (e.g. Astelin) within 2 weeks prior to Visit 1

• Oral or intranasal decongestants within 3 days prior to Visit 1

• Intranasal, oral, or inhaled anticholinergics within 3 days prior to Visit 1

• Oral antileukotrienes within 3 days prior to Visit 1

• Subcutaneous omalizumab (Xolair) within 5 months of Visit 1

• Use of any medications that significantly inhibit the cytochrome P450 subfamilyenzyme CYP3A4, including ritonavir and ketoconazole.

• Ocular antihistamines, artificial tears, eyewashes/nasal irrigation solutions,homeopathic preparations, lubricants, sympathomimetic or vasoconstrictorpreparations during the screening or treatment periods. No exclusion period priorto screening (Visit 1) is required for these treatments.

• Throat treatments (e.g., cough lozenges, throat sprays) during the screening andtreatment periods. No exclusion period prior to screening (Visit 1) is requiredfor these treatments.

• Use of other medications that may affect irritant rhinitis or its symptoms

• Chronic use of concomitant medications, such as tricyclic antidepressants, thatwould affect assessment of the effectiveness of the study drug.

• Chronic use of long-acting beta-agonists (e.g., salmeterol).

• Chronic use of other intranasally administered medications (e.g.,calcitonin-salmon).

• Use of face masks (e.g, general face masks that are used for protection from airpollution, and C-PAP face masks or pillows), saline nasal sprays and lavages, eyedrops, and local, herbal and homeopathic treatments.

• Chronic use of medications that could cause drug-induced rhinitis including:

• ACE inhibitors, reserpine, guanethidine, methyldopa, hydralazine, beta-blockers,alpha-adrenoceptor antagonists (e.g., Prazosin), phentolamine, chlorpromazine,aspirin, and non-steroidal anti-inflammatory medications (NSAIDS). NOTE: Subjects taking aspirin and/or NSAIDs on a chronic basis may be considered forinclusion in the study if the investigator can evaluate and document the subject's irritantrhinitis symptoms are not caused by these medications.

• Use of immunosuppressive medications 8 weeks prior to screening and during the study

• Immunotherapy

• Allergy/Intolerance

• Known hypersensitivity to corticosteroids, or any excipients in the product

• Clinical trial/experimental medication experience

• Exposure to an investigational study drug within 30 days prior to Visit 1

• Participation in a previous or current fluticasone furoate nasal spray (GW685698X) clinical study

• Positive or inconclusive pregnancy test or female who is breastfeeding

• Has a positive or inconclusive pregnancy test at Visit 1 or Visit 2

• Tobacco use

• Subjects who currently use or have used within the past year smoking productsincluding cigarettes, cigars and pipes, or smokeless products such as chewing tobacco.

• Findings of a clinically significant, abnormal electrocardiogram (ECG)

• Findings of a clinically significant laboratory abnormality