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 one allergy medication (0.15% azelastine hydrochloride) is more effective than Placebo alone

Official Title
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Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of MP03-36 in Subjects With Seasonal Allergic Rhinitis

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Drug: Placebo
* Drug: 0.15% azelastine hydrochloride


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, a parent or legal guardian must give written informed consent 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: 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 visit 2, and can include the morning of visit 2) during the Lead-in Period. In addition, 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 visit 2, and can include the morning of visit 2) Willing and able to comply with the study requirements At least a 2-year history of SAR during Texas Mountain Cedar season The presence of IgE-mediated hypersensitivity to Texas Mountain Cedar, 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 any disease or concomitant treatment that could interfere with the interpretation of the study results as determined by the investigator or the sponsor's medical officer. When in doubt, the investigator should confer with the sponsor's medical monitor or designee to determine eligibility for the study. Subjects receiving immunotherapy injections (antigen desensitization) must be on a stable maintenance regimen for at least 30 days before the first study visit (adjustments to regimen following a brief period of missed injections do not preclude participation).Dose reduction when a new bottle is used does not preclude participation. 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 screening visit or randomization visit will disqualify the subjects from the study. Other nasal disease(s) likely to affect deposition of intranasal medication, such as sinusitis, rhinitis medicamentosa, clinically significant polyposis, or clinically significant 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 visit 1. No investigational products are permitted for use during the conduct of this study Presence of any hypersensitivity to drugs similar to azelastine and to either sorbitol or sucralose (Splenda® brand sweetener) 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 visit 1 Respiratory Tract Infections requiring antibiotic treatment 14 days prior to visit 1 Asthma (with the exception of 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 Participation in MedPointe Protocols MP439 or MP440. Employees of the research center / private practice and their family are excluded

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: 1<br>Placebo | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: 2<br>0.15% azelastine hydrochloride | Drug: 0.15% azelastine hydrochloride<br>* 0.15% azelastine hydrochloride 822 mcg<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)for the Entire 14-day Study Period Compared to Placebo (AM and PM Combined)at 14 Days | rTNSS consisting of runny nose, itchy nose, nasal congestion, and sneezing was assessed twice daily. Each symptom is rated on a scale from 0-3: 0=none, 1=mild, 2=moderate, and 3=severe. (maximum 12 points per assessment.) Total possible score is 24 per day. Least square means was controlled for study day as the within-patient effect, treatment group and site as the between-patient effects, treatment by-study day interaction, and basline as a covariate. | baseline and 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Instantaneous Total Nasal Symptom Sscore (AM) for the Entire 14-day Study Period Compared to Placebo | End of 24 hour dosing interval: This endpoint is change from baseline in instantaneous (tNSS) for the 14-day study period compared to placebo to observe if the duration of efficacy lasts 24 hours on a day to day basis. Instantaneous tNSS consists of runny nose, itchy nose, nasal congestion, and sneezing. Each symptom is rated on a scale from 0-3: 0=none, 1=mild, 2=moderate, and 3=severe. Least square means was controlled for study day as the within-patient effect, treatment group and site as the between-patient effects, treatment by-study day interaction, and baseline as a covariate. | baseline to 14 Days | 
| Change From Baseline in Instantaneous Total Nasal Symptom Score for the Entire 14-day Study Period Compared to Placebo (AM and PM Combined) | instantaneous (subjects rate how they feel right now) total nasal symptom score consisting of runny nose, itchy nose, nasal congestion, and sneezing was assessed twice daily. Each symptom is rated on a scale from 0-3: 0=none, 1=mild, 2=moderate, and 3=severe. Total possible score is 24 per day. Least square means was controlled for study day as the within-patient effect, treatment group and site as the between-patient effects, treatment by-study day interaction, and basline as a covariate. | baseline to 14 Days | 
| Change From Baseline in 12-hour Reflective Total Ocular Symptom Score and Instantaneous Total Ocular Symptom Score for the Entire 14-day Study Period Compared to Placebo (AM and PM Combined) | reflective and instantaneous symptom scores (itchy eyes, watery eyes and red eyes) were assessed twice daily. Each symptom is rated on a scale from 0-3: 0=none, 1=mild, 2=moderate, and 3=severe. Total possible TOSS score is 9 per day. Least square means was controlled for study day as the within-patient effect, treatment group and site as the between-patient effects, treatment by-study day interaction, and basline as a covariate. | baseline to14 Days | 
| Change From Baseline to Visit 4 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Compared to Placebo in Subjects 18 Years of Age and Older | A 28-item RQLQ was completed on Day 1 and Day 14 or Early temination. The RQLQ consists of 7 domains rated on a 7 point scale with 0 being not troubled by the allergy symptoms, and 6 being extremely troubled/all of the time. Scores for a series of subsclaes are not combined for a total overall score, rather domain score will be calculated from the mean score of all items in the domain. Overall score will be calculated from the mean score of all items. | 14 Days | 
| Change From Baseline on Direct Visual Nasal Exams to 14 Days | Examination of head and neck (scale: None, Mild, Moderate, Severe) for Epistaxis, Mucosal Edema, Nasal Discharge, Mucosal erythema, Mucosal Bleeding, and Crusting of mucosa. Nasal irratation was rated: 0 = None, Grade 1A = focal irritation, Grade 1B = superficial mucosal erosion, Grade 2 = moderate mucosal erosion,Grade 3 = ulceration, Grade 4 = septal perforation | baseline and 14 days |