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 the combination of two allergy medications (formulated azelastine/fluticasone product)is more effective than placebo or either component 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 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: Placebo
* Drug: azelastineHcl
* Drug: fluticasone propionate
* Drug: azelastine Hcl/fluticasone propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female subjects 12 years of age and older Provide written informed consent/pediatric assent. Subjects must have moderate-to-severe rhinitis, with one or more of the following present: 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 out of a possible 12 and a congestion score of 2 or 3 on Visit 1 Randomization Visit: For the 3 days prior to Randomization and on the morning of Randomization, the sum of the 7 consecutive reflective AM and PM TNSS assessments shall be equal to or greater than 56, with a nasal congestion score equal to or greater than 14 Randomization Visit: instantaneous TNSS score of at least 8 and a congestion score of at least 2 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 requirements At least a 2-year history of SAR during the current allergy season The presence of IgE-mediated hypersensitivity to a prevailing, individual, seasonal pollen, confirmed by a positive response to skin prick within the last year. General good health and free of any 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 (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. 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 Visit 1. 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 Visit 1 Respiratory Tract Infections requiring antibiotic treatment 14 days prior to Visit 1 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, 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. Patients with a history of glaucoma Clinically relevant abnormal physical findings within 1 week of randomization may preclude compliance with the study procedures Employees of the research center or private practice and their family members no more than 50% of their subjects have participated in protocol MP4001, MP4002 or MP4004

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 |
| --- | --- |
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: azelastine Hcl<br> | Drug: azelastineHcl<br>* azelastine hydrochloride 548 mg<br>* Other names: astelin;|
| Active Comparator: fluticasone propionate<br> | Drug: fluticasone propionate<br>* fluticasone propionate 200 mcg<br>|
| Experimental: azelastine Hcl /fluticasone propionate<br> | Drug: azelastine Hcl/fluticasone propionate<br>* azelastine hydrochloride 548 mcg/fluticasone propionate 200 mcg<br>* Other names: MP29-02;|

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 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.An greater negative value is suggestive of improvement. | day 1 to day 14 | 

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 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 score is suggestive of improved condition. | day 1 to day 14 | 
| Change From Baseline in Adult 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 |