Assessment of Fluticasone Propionate on Ocular Allergy Symptoms

Study Overview
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Brief Summary
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This study is designed to investigate the efficacy of fluticasone propionate (FP) on ocular symptoms associated with allergic rhinitis (AR).

Detailed Description
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While the current FP approved indication for GSK marketed formulation is limited to the treatment of nasal symptoms, several large well-controlled studies in which FP maintained adequate control of nasal symptoms when administered in a dose of 200 micrograms (mcg) once-daily (QD) also suggested improvement in ocular symptoms. This study will employ a randomized, double-blind, parallel group, multi-center design that compares FP and placebo nasal sprays in subjects with seasonal allergic rhinitis (SAR) to assess the effectiveness on ocular symptoms associated with AR.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study to Assess the Efficacy of Once-Daily Fluticasone Propionate Aqueous Nasal Spray 200mcg for 14 Days on Ocular Symptoms Associated With Seasonal Allergic Rhinitis

Conditions
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Allergic Rhinitis, Seasonal Allergic Rhinitis

Intervention / Treatment
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* Drug: Fluticasone propionate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with good general health (in the opinion of the investigator) with no clinically significant and relevant abnormalities of medical history Participants with diagnosis of seasonal allergic rhinitis A clinical history (written or verbal confirmation) of allergic rhinitis with the seasonal onset and offset of nasal and ocular allergy symptoms during each of the last 2 mountain cedar pollen allergy seasons. A positive skin test reaction to (at least) the relevant allergen, mountain cedar pollen, as determined by the skin pricks method performed within 12 months of Visit 1). Participants with allergic rhinitis symptom of at least moderate severity for randomization: An iTOSS of ≥ 4 and an iNCSS of ≥2 on the morning of randomization (Visit 3/Baseline). An averaged (rTOSS) of ≥ 4, and an averaged rNCSS of ≥2 for three of the five days during the placebo lead in Participant residing within a geographical environment where exposure to mountain cedar pollen is significant during the entire study period. Participant demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent/assent and has received a signed and dated copy of the informed consent/assent form. Children, ages 12 to 17 will be required to sign an assent form as part of the informed consent process. Exclusion Criteria: Participants with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. Participants with nasal disorders like: injury or surgery to their nose that the investigator believes would interfere with participation in the study. previously diagnosed with a severe physical obstruction of the nose (e.g., deviated septum) that could affect the deposition of double-blind intranasal study drug. Rhinitis medicamentosa Participants who have historical or current evidence of clinically significant uncontrolled disease like asthma, cardiac arrhythmias, hypertension, diabetes mellitus, ocular herpes, glaucoma, hepatic or renal disease, malignancy etc. Presence of or symptoms of an active bacterial or viral infection. Participants who have conjunctivitis caused by an infectious agent. Participants with current, single eye or bilateral cataracts or participants who had cataract surgery within/less than 3 months

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone propionate nasal spray<br>Fluticasone propionate nasal spray with strength per dose of 50 mcg/spray. Two sprays of study treatment per nostril to be administered in morning. | Drug: Fluticasone propionate<br>* Nasal spray formulation (200 mcg/day)<br>* Other names: Flonase;|
| Placebo Comparator: Placebo nasal spray<br>Two sprays of placebo per nostril to be administered in morning. | Drug: Placebo<br>* Vehicle for Fluticasone propionate aqueous nasal spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) | The Reflective Total Ocular Symptom Score (rTOSS) is the sum of 3 individual participant-assessed symptom scores (eye itching/burning, eye tearing/watering, and eye redness), each evaluated using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. Subjects completed rTOSS in the evening (PM rTOSS; 12 hours post morning nasal spray use) and once in the morning (AM score: prior to nasal spray use). Daily (i.e. during one dosing interval) rTOSS is defined as the average of the PM rTOSS and the AM rTOSS of the next day prior to AM dosing. The mean change from baseline in (daily, AM, PM) TOSS was calculated as the subject's treatment period mean (over 14 days; from Day 0 PM to Day 14 AM) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in AM rTOSS | rTOSS is the sum of 3 individual participant-assessed symptom scores (eye itching/ burning, eye tearing/watering, and eye redness), each evaluated using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For AM rToss, subjects completed rTOSS in the morning (AM score: prior to nasal spray use). The mean change from baseline in AM rTOSS was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in PM rTOSS | rTOSS is the sum of 3 individual participant-assessed symptom scores (eye itching/ burning, eye tearing/watering, and eye redness), each evaluated using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For PM rTOSS, subjects completed rTOSS in the evening, 12 hours post morning nasal spray use. The mean change from baseline in PM rTOSS was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in Individual AM Reflective Ocular Symptom Scores for Eye Itching/Burning | The AM Reflective Ocular Symptom Score was assessed individually for eye itching/burning using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For evaluation, subjects completed the scoring in the morning, prior to nasal spray use. The mean change from baseline in AM Reflective Ocular Symptom Score (eye itching and burning) was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in Individual PM Reflective Ocular Symptom Scores for Eye Itching/Burning | The PM Reflective Ocular Symptom Score was assessed individually for eye itching/burning using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For evaluation, subjects completed the scoring in the evening, 12 hours post morning nasal spray use. The mean change from baseline in PM Reflective Ocular Symptom Score (eye itching and burning) was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in Individual AM Reflective Ocular Symptom Scores for Eye Tearing/Watering | The AM Reflective Ocular Symptom Score was assessed individually for eye tearing/watering using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For evaluation, subjects completed the scoring in the morning, prior to nasal spray use. The mean change from baseline in AM Reflective Ocular Symptom Score (eye tearing/watering) was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in Individual PM Reflective Ocular Symptom Scores for Eye Tearing/Watering | The PM Reflective Ocular Symptom Score was assessed individually for eye tearing/watering using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For evaluation, subjects completed the scoring in the evening, 12 hours post morning nasal spray use. The mean change from baseline in PM Reflective Ocular Symptom Score (eye tearing/watering) was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in Individual AM Reflective Ocular Symptom Scores for Eye Redness | The AM Reflective Ocular Symptom Score was assessed individually for eye redness using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For evaluation, subjects completed the scoring in the morning, prior to nasal spray use. The mean change from baseline in AM Reflective Ocular Symptom Score (eye redness) was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in Individual PM Reflective Ocular Symptom Scores for Eye Redness | The PM Reflective Ocular Symptom Score was assessed individually for eye redness using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe, for a possible score of 0-9. For evaluation, subjects completed the scoring in the evening, 12 hours post morning nasal spray use. The mean change from baseline in PM Reflective Ocular Symptom Score (eye redness) was calculated as the subject's treatment period mean (over 14 days) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| Mean Change From Baseline in AM Pre-dose Instantaneous Total Ocular Symptom Scores (iTOSS) | Instantaneous total ocular symptom scores (iTOSS) assessments are self perceived evaluation of symptom severity immediately before the dose (how the subject feels at that point in time). iTOSS (possible score of 0-9) is the sum of 3 individual participant-assessed symptom scores for eye itching/burning, eye tearing/watering, and eye redness each evaluated using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe. Mean changes from baseline were calculated as treatment period iTOSS minus baseline iTOSS. | Baseline to 14 days | 
| Mean Change From Baseline in Reflective Nasal Congestion Symptom Score (rNCSS) | The rNCSS is a participant perceived evaluation of overall congestion symptom severity (evaluated using a scale of 0=None, 1=Mild, 2=Moderate, or 3=Severe) which was completed once in the evening (PM), and once in the morning (AM). rNCSS is defined as the average of the PM rNCSS and the AM rNCSS of the next day prior to AM dosing. The mean change from baseline in rNCSS (daily, AM, PM)was calculated as the subject's treatment period mean (over 14 days; from Day 0 PM to Day 14 AM) minus the baseline period (placebo run-in) mean. | Baseline to 14 days | 
| End-of-treatment Assessment of Response to Therapy for Ocular Symptoms | Overall response to therapy assessment was done using a 7-point categorical scale in which participants rated their response to therapy as follows: +3 = Significantly Improved; +2 = Moderately Improved; +1 = Mildly Improved; 0 = No Change; -1= Mildly Worse; -2 = Moderately Worse; -3 = Significantly Worse. | Day 14 | 
| Mean Change in Objective Assessment of Conjunctival Redness | Conjunctival redness was evaluated as a clinical sign of SAR by the investigator. Scoring of severity was rated according to a 4-point scale: 0 = normal; 1 = Slightly pink; 2 = Moderately pink, some dilation; 3 = Intense red vessels, dilated. | Baseline to 14 days | 
| Mean Changes From Baseline in Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) Scores | MiniRQLQ is a 14-item, disease-specific instrument for assessing the impact of allergic rhinitis on activities of daily living and overall well-being. It measures five domains of functional impairment that are most important to subjects with SAR: practical problems, nasal symptoms, eye symptoms, activity limitations, and other symptoms. Participants scored their degree of impairment on a seven-point scale. (0 - 6). Mini RQLQ final score is the average of sub-scales, ranges from 0 (best possible outcome) to 6 (worst possible outcome). | Baseline to 14 days | 
| Mean Changes From Baseline in Individual MiniRQLQ Scores: Domain - Activities | MiniRQLQ is a 14-item, disease-specific instrument for assessing the impact of allergic rhinitis on activities of daily living and overall well-being. Activity limitations is one of the domains of Mini RQLQ scores. Participants scored their degree of impairment on a seven-point scale (0 = not troubled, 6 = extremely troubled). | Baseline to 14 days | 
| Mean Changes From Baseline in Individual MiniRQLQ Scores: Domain - Practical Problems | MiniRQLQ is a 14-item, disease-specific instrument for assessing the impact of allergic rhinitis on activities of daily living and overall well-being. 'Practical Problems' is one of the domains of Mini RQLQ scores. Participants scored their degree of impairment on a seven-point scale (0 = not troubled, 6 = extremely troubled). | Baseline to 14 days | 
| Mean Changes From Baseline in Individual MiniRQLQ Scores: Domain - Nose Symptoms | MiniRQLQ is a 14-item, disease-specific instrument for assessing the impact of allergic rhinitis on activities of daily living and overall well-being. Nose Symptoms is one of the domains of Mini RQLQ scores. Participants scored their degree of impairment on a seven-point scale (0 = not troubled, 6 = extremely troubled). | Baseline to 14 days | 
| Mean Changes From Baseline in Individual MiniRQLQ Scores: Domain - Eye Symptoms | MiniRQLQ is a 14-item, disease-specific instrument for assessing the impact of allergic rhinitis on activities of daily living and overall well-being. Eye Symptoms is one of the domains of Mini RQLQ scores. Participants scored their degree of impairment on a seven-point scale (0 = not troubled, 6 = extremely troubled). | Baseline to 14 days | 
| Mean Changes From Baseline in Individual MiniRQLQ Scores: Domain - Other Symptoms | MiniRQLQ is a 14-item, disease-specific instrument for assessing the impact of allergic rhinitis on activities of daily living and overall well-being. Other Symptoms is one of the domains of Mini RQLQ scores. Participants scored their degree of impairment on a seven-point scale (0 = not troubled, 6 = extremely troubled). | Baseline to 14 days |