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

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

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

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Drug: Placebo; Drug: 0.1% azelastine hydrochloride 1096 mcg daily; Drug: 0.15% azelastine hydrochloride 1644 mcg daily

• Study Type: Interventional
• Enrollment (Actual): 526
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Oxford, Alabama, United States, 36203
      • Center of Research Excellence, LLC
  • California
    • Encinitas, California, United States, 92024
      • Clinical Research Center
    • Los Angeles, California, United States, 90025
      • Allergy Research Foundation
    • Mission Viejo, California, United States, 92691
      • Southern California Research
    • San Diego, California, United States, 92120
      • Allergy Associates Medical Group Inc
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Storms Clinical Research Institute
    • Denver, Colorado, United States, 80230
      • Colorado Allergy and Asthma Centers
  • Illinois
    • Decatur, Illinois, United States, 62526
      • ENTA Allergy, Head and Neck Associates
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze and Itch Associates
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Family Allergy and Asthma Reserach
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Clinical Research Institute
  • Nebraska
    • Lincoln, Nebraska, United States, 68505
      • Allergy, Asthma and Immunology Associates
  • New Jersey
    • Ocean, New Jersey, United States, 07712
      • Atlantic Research Center
    • Skillman, New Jersey, United States, 08558
      • Princeton Center for Clinical Research
    • Warren, New Jersey, United States, 07059
      • Research Asthma, Sinus and Allergy Centers
  • New York
    • Rochester, New York, United States, 14618
      • AAIR Research Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy, Asthma and Clinical Research Center
  • Pennsylvania
    • Collegeville, Pennsylvania, United States, 19426
      • Allergy and Consultants of NJ/PA
    • Pittsburgh, Pennsylvania, United States, 15241
      • Allergy and Clinical Immunology Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • National Allergy, Asthma and Urticaria of Charleston
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • East Tennesse Center for Clinical Research
  • Texas
    • Austin, Texas, United States, 78731
      • Allergy and Asthma Associates
    • New Braunfels, Texas, United States, 78130
      • Central Texas Health Research
    • San Antonio, Texas, United States, 78229
      • Biogenics Research Institute
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates
    • Waco, Texas, United States, 76708
      • Allergy and Asthma Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female patients 12 years of age and older
2. Provide written informed consent/pediatric assent. If the patient is a minor, a parent or legal guardian must give written informed consent
3. 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
4. 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)
5. Randomization Visit: An instantaneous TNSS of ≥ 8 before beginning the onset of action assessment on Day 1
6. Must have taken at least 10 doses of study medication during the lead-in period
7. Willing and able to comply with the study requirements
8. At least a 2-year history of SAR
9. 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.
10. 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.
11. 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:

1. 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.
2. Other nasal disease(s) likely such as sinusitis, rhinitis medicamentosa, clinically significant polyposis, or nasal structural abnormalities.
3. Nasal surgery or sinus surgery within the previous year.
4. Chronic sinusitis - more than 3 episodes per year
5. Planned travel outside of the study area during the study period
6. 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
7. Presence of any hypersensitivity to drugs similar to azelastine and to either sorbitol or sucralose (Splenda® brand sweetener)
8. Women who are pregnant or nursing
9. Women of childbearing potential who are not abstinent or not practicing a medically acceptable method of contraception
10. Respiratory Tract Infections within 14 days prior to Day -7
11. Respiratory Tract Infections requiring oral antibiotic within 14 days of Day -7
12. Asthma (with the exception of mild, intermittent asthma). Patients with mild, intermittent asthma who only require short-acting inhaled bronchodilators are eligible for enrollment.
13. Significant pulmonary disease including COPD
14. Clinically significant arrhythmia or with symptomatic cardiac conditions
15. A known history of alcohol or drug abuse
16. 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.
17. 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
18. Participation in MedPointe Protocols MP433, MP434, MP435, or MP436.
19. Employees of the research center or private practice and their family members are excluded
20. Patients who received prohibited medications within specified timepoints in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo Nasal Spray; Placebo nasal spray	Drug: Placebo; 0 mcg Placebo daily
EXPERIMENTAL: Astepro 0.1%; 0.1% azelastine hydrochloride nasal spray	Drug: 0.1% azelastine hydrochloride 1096 mcg daily; 0.1% azelastine hydrochloride 1096 mcg daily; Other Names: Astepro 0.1%
EXPERIMENTAL: Astepro 0.15%; 0.15% azelastine hydrochloride nasal spray	Drug: 0.15% azelastine hydrochloride 1644 mcg daily; 0.15% azelastine hydrochloride 1644 mcg daily; Other Names: Astepro 0.15%

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Meda Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): October 1, 2007
• Study Completion (ACTUAL): November 1, 2007

Study Registration Dates

• First Submitted: July 21, 2008
• First Submitted That Met QC Criteria: July 21, 2008
• First Posted (ESTIMATE): July 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 2, 2010
• Last Update Submitted That Met QC Criteria: February 19, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Lipoxygenase Inhibitors; Azelastine
• Other Study ID Numbers: MP438