A Study to Evaluate the Safety and Effectiveness of a Nasal Spray to Treat Seasonal Allergies

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

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).

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Drug: Placebo; Drug: azelastineHcl; Drug: fluticasone propionate; Drug: azelastine Hcl/fluticasone propionate

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 1791
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Allergy, Asthma and Immunology Associates
  • California
    • Encinitas, California, United States, 92024
      • Clinical Research Center
    • Fountain Valley, California, United States, 92708
      • AABI Associates Medical Group
    • Long Beach, California, United States, 90808
      • Allergy & Asthma Care Center of So. Cal
    • 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
    • San Diego, California, United States, 92123
      • Allergy and Asthma Medical Group and Research Center
    • Stockton, California, United States, 95207
      • Bensch Research Associates
    • Walnut Creek, California, United States, 94598
      • Allergy and Asthma Clinical Research, Inc.
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Storms Clinical Research Institute
    • Colorado Springs, Colorado, United States, 80907
      • Asthma and Allergy Associates
    • Denver, Colorado, United States, 80230
      • Colorado Allergy and Asthma Centers
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Clinical Research Atlanta
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze and Itch Associates
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Allergy and Asthma
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Family Allergy and Asthma Reserach
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Reseacrh Institute
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • The Clinical Research Center
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • The Asthma and Allergy Center
  • 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
  • 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
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon, PC
  • 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
    • Austin, Texas, United States, 78759
      • Allergy and Asthma Center of Austin
    • Dallas, Texas, United States, 75231
      • AARA Research Center
    • Dallas, Texas, United States, 75231
      • Pharmaceutical Research & Consulting Inc
    • El Paso, Texas, United States, 79902
      • Western Sky Medical Research
    • New Braunfels, Texas, United States, 78130
      • Central Texas Health Research
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates
    • San Antonio, Texas, United States, 78258
      • Allergy, Asthma Research Center
    • San Antonio, Texas, United States, 78229
      • Diagnostic Research Group
    • Waco, Texas, United States, 76712
      • Allergy Asthma Research Institute
    • Waco, Texas, United States, 76712
      • Allergy and Asthma Center
  • Utah
    • Draper, Utah, United States, 84020
      • Intermountain Clinical Research
  • Washington
    • Seattle, Washington, United States, 98105
      • ASTHMA, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male/female subjects 12 years of age and older
2. Provide written informed consent/pediatric assent.

3. Subjects must have moderate-to-severe rhinitis, with one or more of the following present:

   1. Sleep disturbance
   2. Impairment of daily activities, leisure and/or sport
   3. Impairment of school or work
   4. Troublesome symptoms
4. 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
5. 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
6. 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
7. Have taken at least 10 doses of the lead-in medication
8. Willing and able to comply with the study requirements
9. At least a 2-year history of SAR during the current allergy season
10. The presence of IgE-mediated hypersensitivity to a prevailing, individual, seasonal pollen, confirmed by a positive response to skin prick within the last year.
11. General good health and free of any disease or concomitant treatment that could interfere with the interpretation of the study results.
12. Subjects receiving immunotherapy injections (antigen desensitization) must be on a stable maintenance regimen for at least 30 days before the first study visit
13. Subjects 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 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.
2. Other nasal disease(s) likely to affect deposition of intranasal medication.
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 pollen area during the study period
6. 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
7. Presence of any hypersensitivity to drugs similar to azelastine hydrochloride or fluticasone propionate
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* see section 6.1.1
10. Respiratory Tract Infections within 14 days prior to Visit 1
11. Respiratory Tract Infections requiring antibiotic treatment 14 days prior to Visit 1
12. Asthma (with the exception of intermittent asthma).
13. Significant pulmonary disease including COPD
14. Clinically significant arrhythmia or symptomatic cardiac conditions
15. A known history of alcohol or drug abuse within the last 2 years
16. 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.
17. Patients with a history of glaucoma
18. Clinically relevant abnormal physical findings within 1 week of randomization may preclude compliance with the study procedures
19. Employees of the research center or private practice and their family members
20. no more than 50% of their subjects have participated in protocol MP4001, MP4002 or MP4004

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebo; Placebo
Active Comparator: azelastine Hcl	Drug: azelastineHcl; azelastine hydrochloride 548 mg; Other Names: astelin
Active Comparator: fluticasone propionate	Drug: fluticasone propionate; fluticasone propionate 200 mcg
Experimental: azelastine Hcl /fluticasone propionate	Drug: azelastine Hcl/fluticasone propionate; azelastine hydrochloride 548 mcg/fluticasone propionate 200 mcg; Other Names: MP29-02

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)	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

Collaborators and Investigators

• Sponsor: Meda Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: April 16, 2009
• First Submitted That Met QC Criteria: April 16, 2009
• First Posted (Estimate): April 17, 2009

Study Record Updates

• Last Update Posted (Estimate): June 24, 2013
• Last Update Submitted That Met QC Criteria: June 17, 2013
• Last Verified: June 1, 2013

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; Anti-Inflammatory Agents; Dermatologic Agents; 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; Fluticasone; Xhance; Azelastine
• Other Study ID Numbers: MP4006