Seasonal Allergic Rhinitis, SAR
Conditions
Keywords
Allergies, Hayfever
Brief summary
The purpose of this study is to assess the safety and efficacy of an investigational nasal aerosol at two doses compared with placebo nasal aerosol in the treatment of seasonal allergic rhinitis in children (6-11 years of age).
Interventions
DRUGBDP HFA
BDP (beclomethasone dipropionate) HFA (hydrofluoroalkane) nasal aerosol administered as a single actuation in each nostril daily for the 15 day treatment period. Each actuation contains either 40 or 80 mcg for a total daily dose of either 80 or 160 mcg depending upon the assigned treatment arm.
Placebo formulated as a nasal aerosol spray and administered as a single actuation in each nostril daily for the 15 day treatment period.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects 6 to 11 years of age, as of the Screening Visit (SV) * A documented history of SAR to a relevant seasonal allergen (tree/grass pollen) for a minimum of two years immediately preceding the study Screening Visit (SV). * A demonstrated sensitivity to at least one seasonal allergen (tree/grass pollen) known to induce SAR through a standard skin prick test. * Other criteria apply
Exclusion criteria
* History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations, recent nasal biopsy, nasal trauma (e.g., nasal piercing) or surgery, atrophic rhinitis, or rhinitis medicamentosa (all within the last 60 days prior to the Screening Visit \[SV\]) * History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, chronic sinusitis or influenza,) within the 14 days preceding the Screening Visit (SV), or development of a respiratory infection during the Run-in Period. * Active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta-agonists and any controller drug (e.g., theophylline, leukotriene antagonists). History of intermittent use (less than or equal to 3 uses per week) of inhaled short acting beta-agonists prior to the Screening Visit (SV) is acceptable * Have any conditions that are judged by the investigator to be clinically significant and/or affect the subject's ability to participate in the clinical trial * Other criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment | Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15 | Reflective TNSS is an evaluation of symptom severity over the past 12 hours prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: * 0 = absent (no sign/symptom present) * 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) * 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) * 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported rTNSS over the 4 days prior to randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment | Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15 | Instantaneous TNSS is an evaluation of symptom severity over the last 10 minutes prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: * 0 = absent (no sign/symptom present) * 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) * 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) * 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported iTNSS over the 4 days prior to randomization. |
Countries
United States
Participant flow
Pre-assignment details
A total of 1026 subjects were screened and 906 were enrolled and participated in the Run-in Period. Of the 906 enrolled subjects, 715 were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| BDP HFA 80 mcg/Day Participants/parents administer 40 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days. | 239 |
| BDP HFA 160 mcg/Day Participants/parents administer 80 mcg of beclomethasone dipropionate hydrofluoroalkane (BDP HFA) (one spray per nostril) once daily for 15 days. | 241 |
| Placebo Nasal Aerosol Once Daily Participants/parents administer placebo (a spray with no medication in each nostril) once daily for 15 days. | 234 |
| Total | 714 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Other | 0 | 4 | 3 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo Nasal Aerosol Once Daily | BDP HFA 160 mcg/Day | BDP HFA 80 mcg/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 9.1 years STANDARD_DEVIATION 1.65 | 9.1 years STANDARD_DEVIATION 1.62 | 8.9 years STANDARD_DEVIATION 1.73 | 9.0 years STANDARD_DEVIATION 1.67 |
| Body Mass Index | 19.1 kg/m^2 STANDARD_DEVIATION 4.72 | 19.4 kg/m^2 STANDARD_DEVIATION 4.52 | 19.0 kg/m^2 STANDARD_DEVIATION 4.15 | 19.1 kg/m^2 STANDARD_DEVIATION 4.46 |
| Race/Ethnicity, Customized Asian | 6 participants | 4 participants | 2 participants | 12 participants |
| Race/Ethnicity, Customized Black or African American | 52 participants | 55 participants | 56 participants | 163 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 45 participants | 53 participants | 40 participants | 138 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 189 participants | 188 participants | 199 participants | 576 participants |
| Race/Ethnicity, Customized Other | 12 participants | 10 participants | 12 participants | 34 participants |
| Race/Ethnicity, Customized White | 164 participants | 172 participants | 169 participants | 505 participants |
| Sex: Female, Male Female | 111 Participants | 116 Participants | 105 Participants | 332 Participants |
| Sex: Female, Male Male | 123 Participants | 125 Participants | 134 Participants | 382 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 239 | 0 / 241 | 0 / 234 |
| serious Total, serious adverse events | 0 / 239 | 0 / 241 | 0 / 234 |
Outcome results
Primary
Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment
Reflective TNSS is an evaluation of symptom severity over the past 12 hours prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: * 0 = absent (no sign/symptom present) * 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) * 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) * 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported rTNSS over the 4 days prior to randomization.
Time frame: Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15
Population: The intent to treat (ITT) population included all randomized participants who received at least one dose of randomized study medication and had at least one post-baseline assessment. Two enrolled participants were excluded. One was randomized in error and did not receive test medication. The other provided no post-baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment | -1.9 units on a scale | Standard Error 0.14 |
| BDP HFA 160 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment | -2.0 units on a scale | Standard Error 0.14 |
| Placebo Nasal Aerosol Once Daily | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) During the Two Weeks of Treatment | -1.2 units on a scale | Standard Error 0.14 |
Comparison: The power calculation assumed the standard deviation (SD) for the change from baseline over two weeks in the average of AM and PM reflective TNSS is assumed to be 2.0. Using this standard deviation, 235 subjects per arm provides 90% power to detect a difference of 0.60 in TNSS change from baseline between treatment groups with a two-sided alpha level of 0.05.p-value: <0.00195% CI: [-1.1, -0.3]mixed-model for repeated measures (MMRM)
p-value: <0.00195% CI: [-1.1, -0.4]mixed-model for repeated measures (MMRM)
Secondary
Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment
Instantaneous TNSS is an evaluation of symptom severity over the last 10 minutes prior to the recording of the score. Participants (with assistance from parents/guardians/caregivers, as needed) assessed and recorded four nasal symptoms (runny nose, nasal congestion, nasal itching, and sneezing) twice daily (AM and PM) using the following scale: * 0 = absent (no sign/symptom present) * 1 = mild (sign/symptom clearly present, but minimal awareness; easily tolerated) * 2 = moderate (definite awareness of sign/symptom that is bothersome but tolerable) * 3 = severe (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) The total TNSS scale was 0-12 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the average AM and PM subject-reported iTNSS over the 4 days prior to randomization.
Time frame: Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Day 15
Population: The intent to treat (ITT) population included all randomized participants who received at least one dose of randomized study medication and had at least one post-baseline assessment. Two enrolled participants were excluded. One was randomized in error and did not receive test medication. The other provided no post-baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP HFA 80 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment | -1.6 units on a scale | Standard Error 0.13 |
| BDP HFA 160 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment | -1.7 units on a scale | Standard Error 0.13 |
| Placebo Nasal Aerosol Once Daily | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) During the Two Weeks of Treatment | -1.0 units on a scale | Standard Error 0.13 |
p-value: <0.00195% CI: [-1, -0.3]mixed-model for repeated measures (MMRM)
p-value: <0.00195% CI: [-1.1, -0.4]mixed-model for repeated measures (MMRM)