Seasonal Allergic Rhinitis
Conditions
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
Interventions
DRUGPlacebo
Placebo
DRUGazelastineHcl
azelastine hydrochloride 548 mg
DRUGfluticasone propionate
fluticasone propionate 200 mcg
azelastine hydrochloride 548 mcg/fluticasone propionate 200 mcg
Sponsors
Meda Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | day 1 to day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | day 1 to day 14 | 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. |
| Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | day 1 to day 14 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MP29-02 azelastine HCl 548mcg / fluticasone propionate 200mcg | 448 |
| Azelastine Hcl azelastine HCl nasal spray | 445 |
| Fluticasone Propionate fluticasone propionate nasal spray | 450 |
| Placebo placebo nasal spray | 448 |
| Total | 1,791 |
Baseline characteristics
| Characteristic | MP29-02 | Azelastine Hcl | Fluticasone Propionate | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 57 Participants | 38 Participants | 56 Participants | 46 Participants | 197 Participants |
| Age, Categorical >=65 years | 9 Participants | 17 Participants | 4 Participants | 15 Participants | 45 Participants |
| Age, Categorical Between 18 and 65 years | 382 Participants | 390 Participants | 390 Participants | 387 Participants | 1549 Participants |
| Age Continuous | 35.6 years STANDARD_DEVIATION 14.5 | 36.4 years STANDARD_DEVIATION 14.8 | 34.2 years STANDARD_DEVIATION 14.5 | 34.7 years STANDARD_DEVIATION 14.1 | 35.2 years STANDARD_DEVIATION 14.5 |
| Region of Enrollment United States | 448 participants | 445 participants | 450 participants | 448 participants | 1791 participants |
| Sex: Female, Male Female | 277 Participants | 271 Participants | 280 Participants | 269 Participants | 1097 Participants |
| Sex: Female, Male Male | 171 Participants | 174 Participants | 170 Participants | 179 Participants | 694 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 57 / 448 | 47 / 449 | 32 / 450 | 26 / 451 |
| serious Total, serious adverse events | 1 / 448 | 0 / 449 | 0 / 450 | 1 / 451 |
Outcome results
Primary
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.
Time frame: day 1 to day 14
Population: Intent to Treat (ITT) population includes all subjects who had at least one post baseline dose efficacy evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MP29-02 | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -5.5 units on a scale | Standard Deviation 5.2 |
| Azelastine Hcl | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -4.8 units on a scale | Standard Deviation 4.8 |
| Fluticasone Propionate | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -4.9 units on a scale | Standard Deviation 4.7 |
| Placebo | Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) | -3.4 units on a scale | Standard Deviation 4.3 |
Secondary
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.
Time frame: day 1 to day 14
Population: Intent to Treat (ITT) population includes all subjects who received at least one post baseline efficacy evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MP29-02 | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -5.0 units on a scale | Standard Deviation 5.3 |
| Azelastine Hcl | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -4.3 units on a scale | Standard Deviation 4.9 |
| Fluticasone Propionate | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -4.7 units on a scale | Standard Deviation 4.9 |
| Placebo | Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) | -3.1 units on a scale | Standard Deviation 4.4 |
Secondary
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.
Time frame: day 1 to day 14
Population: Intent to treat (ITT)population includes all subjects(18 years or older) who had at least one post baseline efficacy evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MP29-02 | Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.6 units on a scale | Standard Deviation 1.3 |
| Azelastine Hcl | Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.4 units on a scale | Standard Deviation 1.3 |
| Fluticasone Propionate | Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.6 units on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | -1.0 units on a scale | Standard Deviation 1.2 |