A Study to Evaluate the Safety and Efficacy of Two Nasal Sprays to Treat Seasonal Allergies

Study Overview
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Brief Summary
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The purpose of this study was to determine if two allergy medications are more effective than placebo.

Official Title
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Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of MP03-36 and MP03-33 Compared to Placebo in Patients With Seasonal Allergic Rhinitis

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Drug: 0.15% azelastine hydrochloride 1644 mcg daily
* Drug: 0.1% azelastine hydrochloride 1096 mcg daily
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 12 years of age and older Provide written informed consent/pediatric assent. If the patient 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 Day -7 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. 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 Day 1, and can include the morning of Day 1) Randomization Visit: An instantaneous TNSS of ≥ 8 before beginning the onset of action assessment on Day 1 Must have taken at least 10 doses of study medication during the lead-in period Willing and able to comply with the study requirements At least a 2-year history of SAR The presence of IgE-mediated hypersensitivity to ragweed antigen or other local fall allergens, confirmed by a positive response to either 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 for the skin prick test. 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. Patients 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 does not preclude participation). Patients 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 nasal mucosal erosion, nasal ulceration, or nasal septal perforation at either the screening visit or randomization visit will disqualify the patient from the study. Other nasal disease(s) likely 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 -7. 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 Day -7 Respiratory Tract Infections requiring oral antibiotic within 14 days of Day -7 Asthma (with the exception of mild, intermittent asthma). Patients with mild, intermittent asthma who only require short-acting inhaled bronchodilators are eligible for enrollment. Significant pulmonary disease including COPD Clinically significant arrhythmia or with symptomatic cardiac conditions A known history of alcohol or drug abuse 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 or that might significantly affect the patient's ability to complete 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 MP433, MP434, MP435, or MP436. Employees of the research center or private practice and their family members are excluded Patients who received prohibited medications within specified timepoints in the protocol.

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 Nasal Spray<br>Placebo nasal spray | Drug: Placebo<br>* 0 mcg Placebo daily<br>|
| Experimental: Astepro 0.1%<br>0.1% azelastine hydrochloride nasal spray | Drug: 0.1% azelastine hydrochloride 1096 mcg daily<br>* 0.1% azelastine hydrochloride 1096 mcg daily<br>* Other names: Astepro 0.1%;|
| Experimental: Astepro 0.15%<br>0.15% azelastine hydrochloride nasal spray | Drug: 0.15% azelastine hydrochloride 1644 mcg daily<br>* 0.15% azelastine hydrochloride 1644 mcg daily<br>* Other names: Astepro 0.15%;|

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 | 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 baseline as a covariate. | baseline and 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Instantaneous Total Nasal Symptom Score for the Entire 14-day Study Period Compared to Placebo | 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 and 14 Days | 
| Change From Baseline in the 12-hour Reflective Secondary Symptom Complex Score for the Entire 14-day Study Period Compared to Placebo | Reflective secondary symptom scores (SSCS) (post-nasal drip, itchy eyes, cough and headache) 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 SSCS 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 | 
| Change From Baseline to Day 14 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Compared to Placebo in Patients 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. 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. | baseline and 14 days | 
| Change From Baseline on Direct Visual Nasal Exams | 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 | 14 days |