A Study to Evaluate the Safety and Effectiveness of a Nasal Spray to Treat Seasonal Allergies

Study Overview
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Brief Summary
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The purpose of this study is to determine if two allergy medications (azelastine and fluticasone) are more effective than placebo or either medication alone (azelastine or fluticasone)

Detailed Description
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This will be a Phase III, randomized, double-blind, parallel-group study in subjects with moderate-to-severe SAR. The study will be conducted at 8 investigational sites during the 2007-2008 Texas Mountain Cedar allergy season. After a 7-day Placebo Lead-In Period (Day -7 to Day 1), subjects will be instructed to take placebo lead-in medication twice daily (1 spray per nostril), approximately every 12 hours. On Day 1, subjects who satisfy the symptom severity requirements and continue to meet all of the study inclusion/exclusion criteria will be randomized in a 1:1:1:1 ratio to receive 1 spray per nostril twice daily of MP29-02, azelastine hydrochloride, fluticasone propionate, or placebo nasal spray. Efficacy will be assessed by the change from baseline in the subject-reported 12-hour reflective Total Nasal Symptom Score (TNSS), consisting of the sum of the scores of sneezing, nasal congestion, runny nose, and nasal itching. On Days -7 through 14, subjects will rate the TNSS symptoms, the TOSS symptoms of itchy eyes, watery eyes and eye redness, and the symptom of postnasal drip twice daily (AM and PM) in a diary prior to the dose of study medication. Symptoms will be scored on a 0 to 3 scale (0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms), such that the maximum daily symptom severity score will be 24 for the TNSS and 18 for the TOSS. The 12-hour reflective TNSS, the instantaneous TNSS, the 12-hour reflective score for postnasal drip, the 12-hour reflective TOSS, and the instantaneous TOSS will be calculated based on these scores. Additional secondary efficacy variables will include reflective and individual nasal and ocular symptom scores and change from Baseline to Day 14 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Subjects ≥ 18 years of age will complete the adult RQLQ on Day 1 (prior to dosing) and Day 14. Subjects will return to the clinic on Day 7 for an interim evaluation. After completing the 2-week double-blind treatment period, subjects will return to the clinic on Day 14 (or at time of early termination) for an end-of-study evaluation. Safety and tolerability assessments will be made on Days 7 and 14. Tolerability will be evaluated by subject reported adverse events (AEs), nasal examinations, and vital signs assessments.

Official Title
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Randomized, Double-Blind Trial of MP29-02 Nasal Spray Compared to Placebo, Astelin Nasal Spray, and Fluticasone Propionate Nasal Spray in the Treatment of Patients With Seasonal Allergic Rhinitis

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Drug: MP29-02
* Drug: azelastine Hcl
* Drug: fluticasone propionate
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects 12 years of age and older with a 2 year history of moderate to severe seasonal allergic rhinitis Must be in generally good health Must meet minimum symptom requirements, as specified in the protocol. Must be willing and able to provide informed consent and to participate in all study procedures Positive skin test to a prevalent Texas Mountain Cedar allergen Exclusion Criteria: On Focused Nasal Examination, the presence of any nasal mucosal erosion, nasal ulceration, or nasal septal perforation (Grade 1b - 4) at either the screening visit or randomization visit will disqualify the subject from the study. Other nasal disease(s) likely to affect deposition of intranasal medication, such as sinusitis, rhinitis medicamentosa, clinically significant polyposis, or nasal structural abnormalities. Nasal surgery or sinus surgery within the previous year. Chronic sinusitis - more than 3 episodes per year Planned travel outside of the study area during the study period The use of any investigational drug within 30 days prior to Day screening. No investigational products are permitted for use during the conduct of this study Presence of any hypersensitivity to drugs similar to azelastine hydrochloride or fluticasone propionate Women who are pregnant or nursing Women of childbearing potential who are not abstinent or not practicing a medically acceptable method of contraception* see section 6.1.1 Respiratory Tract Infections within 14 days prior to Day screening Respiratory Tract Infections requiring antibiotic treatment 14 days prior to screening Asthma (with the exception of mild, intermittent asthma). Subjects with mild, intermittent asthma who only require short-acting inhaled bronchodilators (not more often than twice per week) and who do not have nocturnal awakening as a result of asthma are eligible for enrollment Significant pulmonary disease including COPD Clinically significant arrhythmia or symptomatic cardiac conditions A known history of alcohol or drug abuse within the last 2 years Existence of any surgical or medical condition or physical or laboratory findings, which in the opinion of the investigator or sponsor's medical monitor, might significantly alter the absorption, distribution, metabolism, or excretion of study drug; that might significantly affect the subject's ability to complete this trial; or their safety in this trial. Clinically relevant abnormal physical findings within 1 week of randomization which, in the opinion of the investigator, would interfere with the objectives of the study or that may preclude compliance with the study procedures

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP29-02<br>azelastine HCl 548 mcg / fluticasone propionate 200 mcg nasal spray | Drug: MP29-02<br>* azelastine HCl 548 mcg / fluticasone propionate 200 mcg nasal spray one spray per nostril twice a day<br>|
| Active Comparator: azelastine Hcl 548 mcg<br>azelastine Hcl 548 mcg nasal spray | Drug: azelastine Hcl<br>* azelastine Hcl nasal spray one spray per nostril two times a day<br>* Other names: Astelin;|
| Active Comparator: fluticasone propionate 200 mcg<br>fluticasone propionate 200 mcg nasal spray | Drug: fluticasone propionate<br>* fluticasone propionate 200 mcg nasal spray one spray per nostril two times a day<br>* Other names: generic Flonase;|
| Placebo Comparator: placebo<br>placebo nasal spray | Drug: placebo<br>* placebo nasal spray one spray per nostril two times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | change from baseline in the 12 hour reflective total nasal symptoms score(rTNSS) consisting of nasal congestion,runny nose,itchy nose and sneezing scored twice daily( AM and PM) in diary cards for the entire 14 day study period The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value. | day 1 to day14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | change from baseline in the 12 hour instantaneous total nasal symptoms score(iTNSS) consisting of nasal congestion,runny nose,itchy nose and sneezing scored twice daily( AM and PM) in diary cards for the entire 14 day study period. The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value. | day 1 to day 14 | 
| Change From Baseline in Adult ( Greater Than 18 Years of Age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the End of 14 Days | Change from Baseline in adult ( greater than 18 years of age) Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)at the end of 14 days The measurement scale is 0 to 24. A reduction in symptom severity score is indicated by a negative value. | day 1 to day 14 |