A Study Evaluating 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 (formulated azelastine and fluticasone product) 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, placebo-controlled, parallel-group study in subjects with moderate-to-severe seasonal allergic rhinitis (SAR). The study will begin with a 7-day, single-blind, 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). On Days 1 through 14, subjects will rate the instantaneous and reflective TNSS symptoms of sneezing, nasal congestion, runny nose, and nasal itching; the instantaneous and reflective total ocular symptom score (TOSS) symptoms of itchy eyes, watery eyes and eye redness; the symptom of postnasal drip will be rated, reflectively, 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. Additional secondary efficacy variables will include reflective individual nasal and ocular symptom scores, as well as change from Baseline to Day 14 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Subjects ≥ 18 years of age will complete the 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, Azelastine Hydrochloride 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: azelastine HCl/fluticasone propionate
* 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 Provide written informed consent/pediatric assent. If the subject is a minor, parent or legal guardian must give written informed consent Subjects must have moderate-to-severe rhinitis, defined as having one or more of the following: Sleep disturbance Impairment of daily activities, leisure and/or sport Impairment of school or work Troublesome symptoms Screening Visit: Have a 12-hour reflective TNSS of at least 8 of 12 and a congestion score of 2 or 3 on Visit 1 Randomization Visit: Have a 12-hour reflective TNSS (AM or PM) of at least 8 on 3 separate symptom assessments (one of which was within 2 days of Day 1, and can include the morning of Day 1) during the Lead-in Period. Randomization Visit: Have an AM or PM 12-hour reflective nasal congestion score of 2 or 3 must have been recorded on 3 separate symptom assessments (one of which was within 2 days of Day 1, and can include the morning of Day 1) Randomization Visit: Have an instantaneous TNSS score of 8 or more at time point zero, just prior to beginning the onset of action assessment Have taken at least 10 doses of the lead-in medication Willing and able to comply with the study requirementsAt least a 2-year history of SAR during Fall allergy season The presence of IgE-mediated hypersensitivity to a local Fall pollen, confirmed by a positive response to skin prick within the last year. A positive response is defined as a wheal diameter of at least 3 mm larger than the negative control. General good health and free of disease or concomitant treatment that could interfere with the interpretation of the study results Subjects receiving immunotherapy injections (antigen desensitization) must be on a stable maintenance regimen for at least 30 days before the first study visit Subjects currently receiving sublingual immunotherapy are excluded. A 6-month washout period is required following the last dose of sublingual immunotherapy. Exclusion Criteria: On Focused Nasal Examination, the presence of any superficial and moderate nasal mucosal erosion, nasal mucosal ulceration, or nasal septum perforation at either the screening visit or randomization visit Other nasal disease(s) likely to affect deposition of intranasal medication Nasal surgery or sinus surgery within the previous year. Chronic sinusitis - more than 3 episodes per year Planned travel outside of the pollen area during the study period The use of any investigational drug within 30 days prior to Day -7. 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* Respiratory Tract Infections within 14 days prior to Day -7 Respiratory Tract Infections requiring antibiotic treatment 14 days prior to Day -7 Asthma (with the exception of intermittent asthma). 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 that could interfere with study result interpretation. Patients with a history of Glaucoma Clinically relevant abnormal physical findings within 1 week of randomization that may preclude compliance with the study procedures Employees of the research center or private practice and their family members are excluded Subjects who participated in protocol MP4001 or MP4002

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: azelastine HCl/fluticasone propionate<br>nasal spray | Drug: azelastine HCl/fluticasone propionate<br>* azelastine HCl 548 mcg/ fluticasone propionate 200 mcg one spray per nostril BID<br>* Other names: MP29-02;|
| Active Comparator: azelastine HCL<br>nasal spray | Drug: azelastine Hcl<br>* azelastine Hcl 548 mcg one spray per nostril BID<br>* Other names: azelastine hydrochloride;|
| Active Comparator: fluticasone propionate<br>nasal spray | Drug: fluticasone propionate<br>* fluticasone propionate 200 mcg one spray per nostril BID<br>|
| Placebo Comparator: placebo<br>nasal spray | Drug: placebo<br>* placebo one spray per nostril BID<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 12-hour reflective(how you felt over the previous 12 hours) total nasal symptom 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.A greater negative score is suggestive of improvement. | day1 to 14 days | 

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 12-hour instantaneous ( how do you feel now) total nasal symptom 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.A greater negative value is suggestive of improvement. | day 1 to14 | 
| Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scored at day 1(baseline) and at day 14.The scale is measured from a value of 0 to 24. A negative number corresponds to a change from baseline measurement. An increased negative number is suggestive of improvement. | day 1 to day 14 |