Seasonal Allergic Rhinitis
Conditions
Brief summary
To compare safety and efficacy of Perrigo's steroid drug product compared with an FDA approved steroid drug product in the treatment of subjects with seasonal allergic rhinitis.
Interventions
DRUGAzelastine Hydrochloride/Fluticasone Propionate Nasal Spray
137 micro-grams Azelastine Hydrochloride, 50 micro-grams Fluticasone Propionate
DRUGPlacebo nasal spray
Placebo nasal spray
Sponsors
Padagis LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Complete the informed consent/assent process. 2. Male or female between 12 to 65 years of age, inclusive. 3. Females of childbearing potential willing to use an acceptable form of birth control during the study. 4. Moderate-to-severe allergic rhinitis. 5. At Visits 1 and 2 have instantaneous and reflective symptom scores sufficient enough to qualify for continued participation in the study 6. Subject must have a history (for 2 or more seasons) of seasonal allergy to at least one allergen known to be present during the study season. 7. Subject must be in general good health with no clinically significant disease or medical procedure other than allergic rhinitis within various time periods prior to Visit 1. 8. Subject must be willing and able to understand and comply with the requirements of the study
Exclusion criteria
1. Female who is pregnant or nursing, who is not using or does not agree to use an acceptable form of contraception during the study, or who intends to become pregnant during the study. 2. Subject has a history of hypersensitivity or allergy to any ingredient in the drug products. 3. Subject has any condition or abnormality of the upper airway that, in the opinion of the Investigator, could interfere with administration of the product, evaluation of the subject's condition, or other aspect of the trial. 4. The presence of any nasal mucosal crusting, erosion, ulceration, nasal septum perforation, or any kind of blockage of the nasal passages at screening or randomization. 5. Subject has asthma or a history of asthma requiring chronic treatment within two years of Visit 1. 6. Treatment for oral Candidiasis within 30 days of starting the study, or a current oral Candidiasis infection. 7. Subject has had recent exposure (30 days) or is at risk of being exposed to chicken pox or measles. 8. Subjects with any untreated fungal, bacterial, systemic viral infections within the previous 30 days. 9. Use of various therapies within the given time period prior to Visit 1 and throughout the study. 10. Initiation of hormone replacement therapy during the study. 11. Initiation of immunotherapy during the study, or changes in dosage or frequency of immunotherapy within the 30 days preceding Visit 1. 12. Subject has received immune-system therapy or peptide immunotherapy of any form. 13. Subject had desensitization therapy to the seasonal allergen that is causing their allergic rhinitis within the previous 6 months. 14. Subject presented with conjunctivitis or any other eye signs/symptoms that are not related to the diagnosis of SAR. 15. Clinically relevant abnormal physical findings or medication use within 1 week of randomization, which, in the opinion of the investigator, might interfere with the conduct or results of the study or place the prospective subject at increased risk. 16. Subjects being treated with a product containing a sympathomimetic agent. 17. Subject has previously enrolled in this study or is enrolled in this study with another participating investigator site. 18. Subject is concurrently participating in another investigational study or using any investigational drug (or biologic) or device. 19. Subject plans or anticipates travel outside the local allergen area at any point in the study. 20. History of unresponsiveness to steroid nasal sprays for SAR symptoms. 21. Employee (or employee's family member) of the research center or private practice. 22. If the subject has a smoking history of greater than 10 pack years or has recently started or re-started smoking within the past 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline for Mean Reflective Total Nasal Symptom Score (rTNSS) | Day 1 through Day 14 | The symptoms included in the reflective Total Nasal Symptom Score (rTNSS) scale are nasal congestion/stuffy nose, nasal discharge/runny nose, sneezing, and itchy nose. Symptoms were scored on a four point scale, 0-3, for each assessment were calculated by totaling these four symptom scores for a maximum score of 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Mean Instantaneous Total Nasal Symptom Score (iTNSS) | Day 1 through Day 14 | The symptoms included in the instantaneous Total Nasal Symptom Score (iTNSS) scale are nasal congestion/stuffy nose, nasal discharge/runny nose, sneezing, and itchy nose. Symptoms were scored on a four point scale, 0-3, for each assessment were calculated by totaling these four symptom scores for a maximum score of 12. |
| Change From Baseline iTNSS Scores on Day 1 Post First Randomized Dose | Day 1, up to four hours post the first dose | This outcome measured the time to statistical significance of the reduction of signs/symptoms over a 4 hour period on Day 1 only by measuring the reduction in iTNSS scores. When the change from baseline was statistically significant, it was associated with a time to onset of the anti-histamine component of the formulation. Subjects will record iTNSS scores for 4 hours post first randomized dose. The symptoms included in the instantaneous Total Nasal Symptom Score (iTNSS) scale are nasal congestion/stuffy nose, nasal discharge/runny nose, sneezing, and itchy nose. Symptoms were scored on a four point scale, 0-3, for each assessment were calculated by totaling these four symptom scores for a maximum score of 12. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test Product Azelastine Hydrochloride/Fluticasone Propionate Nasal Spray
Azelastine Hydrochloride/Fluticasone Propionate Nasal Spray: 137 micro-grams Azelastine Hydrochloride, 50 micro-grams Fluticasone Propionate | 381 |
| Reference Product Azelastine Hydrochloride/Fluticasone Propionate Nasal Spray: 137 micro-grams Azelastine Hydrochloride, 50 micro-grams Fluticasone Propionate | 376 |
| Placebo Product Placebo nasal spray
Placebo nasal spray | 194 |
| Total | 951 |
Baseline characteristics
| Characteristic | Test Product | Reference Product | Placebo Product | Total |
|---|---|---|---|---|
| Age, Continuous | 37.5 years STANDARD_DEVIATION 12.87 | 38.6 years STANDARD_DEVIATION 13.28 | 38.4 years STANDARD_DEVIATION 13.07 | 38.1 years STANDARD_DEVIATION 13.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 59 Participants | 30 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 329 Participants | 316 Participants | 164 Participants | 809 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 85 Participants | 81 Participants | 41 Participants | 207 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) White | 283 Participants | 285 Participants | 148 Participants | 716 Participants |
| Sex: Female, Male Female | 250 Participants | 248 Participants | 123 Participants | 621 Participants |
| Sex: Female, Male Male | 131 Participants | 128 Participants | 71 Participants | 330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 381 | 0 / 376 | 0 / 194 |
| other Total, other adverse events | 0 / 381 | 0 / 376 | 0 / 194 |
| serious Total, serious adverse events | 3 / 381 | 1 / 376 | 0 / 194 |
Outcome results
Primary
Mean Change From Baseline for Mean Reflective Total Nasal Symptom Score (rTNSS)
The symptoms included in the reflective Total Nasal Symptom Score (rTNSS) scale are nasal congestion/stuffy nose, nasal discharge/runny nose, sneezing, and itchy nose. Symptoms were scored on a four point scale, 0-3, for each assessment were calculated by totaling these four symptom scores for a maximum score of 12.
Time frame: Day 1 through Day 14
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Mean Change From Baseline for Mean Reflective Total Nasal Symptom Score (rTNSS) | -2.95 score on a scale | Standard Error 0.15 |
| Reference Product | Mean Change From Baseline for Mean Reflective Total Nasal Symptom Score (rTNSS) | -3.13 score on a scale | Standard Error 0.15 |
| Placebo Nasal Spray | Mean Change From Baseline for Mean Reflective Total Nasal Symptom Score (rTNSS) | -1.98 score on a scale | Standard Error 0.19 |
90% CI: [84.77, 104.52]Trial and Error approach
Secondary
Change From Baseline iTNSS Scores on Day 1 Post First Randomized Dose
This outcome measured the time to statistical significance of the reduction of signs/symptoms over a 4 hour period on Day 1 only by measuring the reduction in iTNSS scores. When the change from baseline was statistically significant, it was associated with a time to onset of the anti-histamine component of the formulation. Subjects will record iTNSS scores for 4 hours post first randomized dose. The symptoms included in the instantaneous Total Nasal Symptom Score (iTNSS) scale are nasal congestion/stuffy nose, nasal discharge/runny nose, sneezing, and itchy nose. Symptoms were scored on a four point scale, 0-3, for each assessment were calculated by totaling these four symptom scores for a maximum score of 12.
Time frame: Day 1, up to four hours post the first dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Change From Baseline iTNSS Scores on Day 1 Post First Randomized Dose | -3.41 units on a scale | Standard Error 0.15 |
| Reference Product | Change From Baseline iTNSS Scores on Day 1 Post First Randomized Dose | -3.29 units on a scale | Standard Error 0.15 |
| Placebo Nasal Spray | Change From Baseline iTNSS Scores on Day 1 Post First Randomized Dose | -2.94 units on a scale | Standard Error 0.2 |
Secondary
Mean Change From Baseline in the Mean Instantaneous Total Nasal Symptom Score (iTNSS)
The symptoms included in the instantaneous Total Nasal Symptom Score (iTNSS) scale are nasal congestion/stuffy nose, nasal discharge/runny nose, sneezing, and itchy nose. Symptoms were scored on a four point scale, 0-3, for each assessment were calculated by totaling these four symptom scores for a maximum score of 12.
Time frame: Day 1 through Day 14
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Mean Change From Baseline in the Mean Instantaneous Total Nasal Symptom Score (iTNSS) | -2.81 score on a scale | Standard Error 0.15 |
| Reference Product | Mean Change From Baseline in the Mean Instantaneous Total Nasal Symptom Score (iTNSS) | -2.96 score on a scale | Standard Error 0.15 |
| Placebo Nasal Spray | Mean Change From Baseline in the Mean Instantaneous Total Nasal Symptom Score (iTNSS) | -1.88 score on a scale | Standard Error 0.19 |
90% CI: [84.86, 105.54]Trial and Error approach