Clinical trial NCT00883168: A Study to Evaluate the Safety and Effectiveness of a Nasal Spray to Treat Seasonal Allergies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Seasonal Allergic Rhinitis
Lead sponsor: Meda Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-04-17
Enrollment: 1791
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS)
timeFrame: day 1 to day 14
Secondary outcomes:
measure: Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS)
timeFrame: day 1 to day 14
measure: Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
timeFrame: day 1 to day 14
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Allergy, Asthma and Immunology Associates
state: Arizona
city: Encinitas
country: United States
facility: Clinical Research Center
state: California
city: Fountain Valley
country: United States
facility: AABI Associates Medical Group
state: California
city: Long Beach
country: United States
facility: Allergy & Asthma Care Center of So. Cal
state: California
city: Los Angeles
country: United States
facility: Allergy Research Foundation
state: California
city: Mission Viejo
country: United States
facility: Southern California Research
state: California
city: San Diego
country: United States
facility: Allergy Associates Medical Group Inc
state: California
city: San Diego
country: United States
facility: Allergy and Asthma Medical Group and Research Center
state: California
city: Stockton
country: United States
facility: Bensch Research Associates
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research, Inc.
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates
state: Colorado
city: Colorado Springs
country: United States
facility: Storms Clinical Research Institute
state: Colorado
city: Denver
country: United States
facility: Colorado Allergy and Asthma Centers
state: Colorado
city: Atlanta
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Normal
country: United States
facility: Sneeze, Wheeze and Itch Associates
state: Illinois
city: Overland Park
country: United States
facility: Kansas City Allergy and Asthma
state: Kansas
city: Louisville
country: United States
facility: Family Allergy and Asthma Reserach
state: Kentucky
city: North Dartmouth
country: United States
facility: Northeast Medical Research Associates
state: Massachusetts
city: Minneapolis
country: United States
facility: Clinical Reseacrh Institute
state: Minnesota
city: St. Louis
country: United States
facility: The Clinical Research Center
state: Missouri
city: Papillion
country: United States
facility: The Asthma and Allergy Center
state: Nebraska
city: Ocean
country: United States
facility: Atlantic Research Center
state: New Jersey
city: Skillman
country: United States
facility: Princeton Center for Clinical Research
state: New Jersey
city: Warren
country: United States
facility: Research Asthma, Sinus and Allergy Centers
state: New Jersey
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research Center
state: Oklahoma
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Collegeville
country: United States
facility: Allergy and Consultants of NJ/PA
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: Charleston
country: United States
facility: National Allergy, Asthma and Urticaria of Charleston
state: South Carolina
city: Knoxville
country: United States
facility: East Tennesse Center for Clinical Research
state: Tennessee
city: Austin
country: United States
facility: Allergy and Asthma Associates
state: Texas
city: Austin
country: United States
facility: Allergy and Asthma Center of Austin
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting Inc
state: Texas
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: San Antonio
country: United States
facility: Diagnostic Research Group
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
city: San Antonio
country: United States
facility: Allergy, Asthma Research Center
state: Texas
city: Waco
country: United States
facility: Allergy and Asthma Center
state: Texas
city: Waco
country: United States
facility: Allergy Asthma Research Institute
state: Texas
city: Draper
country: United States
facility: Intermountain Clinical Research
state: Utah
city: Seattle
country: United States
facility: Asthma, Inc.
state: Washington
Study officials:
affiliation: Meda Pharmaceuticals
name: Lewis M Fredane, MD
role: STUDY_DIRECTOR
References: