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

Meda Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Seasonal Allergic Rhinitis

Treatments: Drug: fluticasone propionate; Drug: Placebo; Drug: azelastineHcl; Drug: azelastine Hcl/fluticasone propionate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00883168

MP4006

Details and patient eligibility

About

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).

Full 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

Enrollment: 1,791 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,791 participants in 4 patient groups, including a placebo group

placebo

Placebo Comparator group

Treatment:

Drug: Placebo

azelastine Hcl

Active Comparator group

Treatment:

Drug: azelastineHcl

fluticasone propionate

Active Comparator group

Treatment:

Drug: fluticasone propionate

azelastine Hcl /fluticasone propionate

Experimental group

Treatment:

Drug: azelastine Hcl/fluticasone propionate