Allergic Rhinitis
Conditions
Keywords
allergic rhinitis, pediatric subjects, BDP nasal aerosol
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Beclomethasone dipropionate (BDP) nasal aerosol in subjects with Perennial Allergic Rhinitis (PAR).
Interventions
DRUGBDP Nasal Aerosol
DRUGPlacebo
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
4 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects 4 to 11 years of age, inclusive, as of the Screening Visit (SV). * A documented history of PAR to a relevant perennial allergen for a minimum of 12 months (6 months for subjects 4 to 5 years of age) immediately preceding the study Screening Visit (SV). * A demonstrated sensitivity to at least one allergen known to induce PAR 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 of the following 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) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age | Baseline (Day -4 to Day 1 predose), Day 1 (postdose) to Week 6 | 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 and the during study rTNSS values were defined as the average AM and PM subject-reported rTNSS during each time period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age | Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Week 6 | 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 and the during study iTNSS values were defined as the average AM and PM subject-reported iTNSS during each time period. |
| Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age | Baseline (Day -4 to Day 1 predose), Day 1 (postdose) to Week 6 | 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 and the during study rTNSS values were defined as the average AM and PM subject-reported rTNSS during each time period. |
| Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age | Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Week 6 | 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 and the during study iTNSS values were defined as the average AM and PM subject-reported iTNSS during each time period. |
Countries
United States
Participant flow
Pre-assignment details
A total of 770 subjects were screened. The 547 participants were randomly assigned to either BDP nasal aerosol (80 mcg/day) or placebo nasal aerosol in a 2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| BDP Nasal Aerosol 80 mcg/Day BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period. | 362 |
| Placebo Nasal Aerosol Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period. | 185 |
| Total | 547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 8 | 3 |
| Overall Study | Non-compliance | 4 | 0 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 11 | 8 |
Baseline characteristics
| Characteristic | BDP Nasal Aerosol 80 mcg/Day | Placebo Nasal Aerosol | Total |
|---|---|---|---|
| Age, Continuous | 8.0 years STANDARD_DEVIATION 2.16 | 8.0 years STANDARD_DEVIATION 2.23 | 8.0 years STANDARD_DEVIATION 2.18 |
| Age, Customized 4 to 5 years | 62 participants | 31 participants | 93 participants |
| Age, Customized 6 to 11 years | 300 participants | 154 participants | 454 participants |
| Body Mass Index | 18.6 kg/m^2 STANDARD_DEVIATION 4.22 | 18.9 kg/m^2 STANDARD_DEVIATION 4.33 | 18.7 kg/m^2 STANDARD_DEVIATION 4.25 |
| Race/Ethnicity, Customized Black | 65 participants | 25 participants | 90 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 144 participants | 75 participants | 219 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 217 participants | 110 participants | 327 participants |
| Race/Ethnicity, Customized Other | 25 participants | 15 participants | 40 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 272 participants | 145 participants | 417 participants |
| Sex: Female, Male Female | 175 Participants | 71 Participants | 246 Participants |
| Sex: Female, Male Male | 187 Participants | 114 Participants | 301 Participants |
| Weight | 33.4 kg STANDARD_DEVIATION 13.4 | 33.8 kg STANDARD_DEVIATION 13.24 | 33.5 kg STANDARD_DEVIATION 13.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 362 | 21 / 185 |
| serious Total, serious adverse events | 0 / 362 | 0 / 185 |
Outcome results
Primary
Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age
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 and the during study rTNSS values were defined as the average AM and PM subject-reported rTNSS during each time period.
Time frame: Baseline (Day -4 to Day 1 predose), Day 1 (postdose) to Week 6
Population: Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of randomized study medication and had at least 1 post-baseline subject-reported rTNSS assessment. Subpopulation of study participants aged 6-11 years.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age | -2.26 units on a scale | Standard Error 0.12 |
| Placebo Nasal Aerosol | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age | -1.60 units on a scale | Standard Error 0.17 |
Comparison: Based on other studies, the standard deviation for the change from baseline over the first 6 weeks of treatment in the average of AM and PM rTNSS is assumed to be 2.0. Using this standard deviation, 450 subjects aged 6 to 11 years (300 on active treatment of BDP and 150 on placebo) provide approximately 90% power to detect a difference of 0.65 in rTNSS change from baseline between treatment groups with a two-sided alpha level of 0.05.p-value: 0.00295% CI: [-1.08, -0.24]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) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age
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 and the during study iTNSS values were defined as the average AM and PM subject-reported iTNSS during each time period.
Time frame: Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Week 6
Population: Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of randomized study medication and had at least 1 post-baseline subject-reported rTNSS assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age | -2.07 units on a scale | Standard Error 0.11 |
| Placebo Nasal Aerosol | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age | -1.53 units on a scale | Standard Error 0.15 |
p-value: 0.00495% CI: [-0.91, -0.17]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) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age
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 and the during study iTNSS values were defined as the average AM and PM subject-reported iTNSS during each time period.
Time frame: Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Week 6
Population: Full analysis set (FAS). Subpopulation of study participants aged 6-11 years.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age | -1.98 units on a scale | Standard Error 0.12 |
| Placebo Nasal Aerosol | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age | -1.39 units on a scale | Standard Error 0.17 |
p-value: 0.00495% CI: [-0.99, -0.18]mixed-model for repeated measures (MMRM)
Secondary
Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age
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 and the during study rTNSS values were defined as the average AM and PM subject-reported rTNSS during each time period.
Time frame: Baseline (Day -4 to Day 1 predose), Day 1 (postdose) to Week 6
Population: Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of randomized study medication and had at least 1 post-baseline subject-reported rTNSS assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age | -2.32 units on a scale | Standard Error 0.11 |
| Placebo Nasal Aerosol | Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age | -1.71 units on a scale | Standard Error 0.16 |
p-value: 0.00295% CI: [-1, -0.23]mixed-model for repeated measures (MMRM)