Rhinitis, Allergic, Perennial
Conditions
Brief summary
The primary objective of the study was to characterize the difference in prepubescent growth velocity in children 3 to 9 years of age with perennial allergic rhinitis (PAR) treated with triamcinolone acetonide (TAA) nasal spray (NASACORT® AQ 110 μg treatment group) or placebo (NASACORT® AQ placebo group) for 12-months. The secondary objectives were to compare the following in prepubertal participants treated with TAA nasal spray versus placebo: * the 24-hour urinary free cortisol levels and the cortisol/creatinine ratio (to measure the Hypothalamic-Pituitary Adrenal \[HPA\] axis function) * the rate of treatment-emergent-adverse-events (TEAE) * global efficacy rated by the investigator and the participant separately * the rate of use of rescue medication during the study
Detailed description
The study consisted of: * a 4- to 6-month screening/baseline period * a 12-month (up to Day 360+/-5 days) double-blind treatment period starting on Day 1 * a 2-month follow-up period (up to Day 420+/-5 days)
Interventions
OTHERPlacebo
Placebo to TAA-AQ was administered once at the study site in each nostril during the baseline/screening period to demonstrate intranasal IP administration
DRUGTAA-AQ, Nasacort® AQ
110 μg TAA-AQ was administered once daily intranasally (1 spray delivering 55 μg of TAA-AQ in each nostril) during the double-blind treatment period
DRUGClaritin®
Participants were provided Children's Claritin® Syrup (5 mg of loratadine per 5 mL), as rescue medication for the relief of allergic rhinitis (AR) symptoms, and could be used throughout the study on an as needed basis according to the Food and Drug Administration-approved manufacturer's label
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
Participants meeting the following eligibility criteria were enrolled. Inclusion criteria: 1. Male participants \[3 years to \<= 9 years + 0 days old\] at Visit 1 and no older than \[9 years + 120 days\] at Visit 3; and, female participants \[3 years to \<= 8 years + 0 days old\] at Visit 1 and no older than \[8 years + 120 days\] at Visit 3: all sexually prepubertal (ie, Stage 1 of Tanner Classification of sexual maturity) at Visit 1 and Visit 3. A 5-day extension to the age upper bound was permitted under certain circumstances to enable scheduling of Visits 1 and 3 2. At least a one year history of PAR as assessed and documented by the investigator (with or without seasonal allergic rhinitis \[SAR\]) 3. Positive skin test (prick or intradermal) to a perennial allergen that was present in the participant's environment. A skin test was considered positive if the wheal produced by the allergen was equal to or greater than that caused by positive control (histamine) or was at least 3 mm (prick test) or 7 mm (intradermal test) greater than the wheal of negative control (saline). If a skin test could not be performed, the radioallergosorbent test (RAST) would be used as an alternative. Documented historical skin testing or RAST performed during the past year were acceptable 4. Height within the 3rd and 97th percentiles at screening (Visit 1), Visit 2, and at randomization (Visit 3) 5. Symptomatic (daily AM instantaneous total nasal symptom score was \>= 4 out of 12) on any 4 out of the last 7 consecutive days immediately prior to and including the morning of Visit 3. Symptom ratings were to be completed with the help of a parent/guardian/caregiver 6. Written informed consent and ability of parent or legal guardian of the participant to give a written informed consent before any study related procedures. Participants 7 years of age and older must have provided a signed assent form 7. Participants had to be toilet-trained
Exclusion criteria
1. Gross nasal anatomical deformities including large polyposis and marked deviated septum 2. History of or current cataract or glaucoma 3. History of hypersensitivity to the corticosteroids or to any excipient of the investigational product 4. Participant was the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol 5. Height, weight, or body mass index (BMI)-for-age below the 3rd or above the 97th percentile at Visits 1, 2, or 3 6. Treatment with systemic corticosteroids (oral, intravenous, intramuscular, or intra-articular) within 3 months prior to Visit 1 7. Treatment with systemic corticosteroids for \>2 courses received up to 1 year before Visit 1 was exclusionary. Up to 2 courses of systemic corticosteroids each course not exceeding 14 days up to 1 year before Visit 1 was allowed. 8. Treatment with inhaled, intranasal, or high potency topical corticosteroid exposure within 6 weeks prior to Visit 1. Mild asthma that was well-controlled and without the use of inhaled corticosteroids within 6 weeks before screening (Visit 1). 9. Immunotherapy, except stable (\>=1 month) maintenance schedule before Visit 1. 10. Treatment with any substance before Visit 1 that might have affected growth velocity and/or linear growth, such as, but not be limited to methylphenidate hydrochloride, thyroid hormone, growth hormone, anabolic steroids, calcitonin, estrogens, progestins, bisphosphonates, anticonvulsants, or phosphate-binding antacids 11. Treatment with any investigational product or device in the 30 days before Visit 1 or at any time throughout the duration of this trial (Visit 1 through Visit 11). 12. Bone age as assessed by X-ray of the left hand and wrist that was outside +/- 1.5 years of participants chronological age at Visit 2. Right hand and wrist were to be radiographed in the event of bone injury to the left hand or wrist. 13. Unresolved upper respiratory tract infection, sinus infection or nasal candidiasis (i.e., symptomatic or under treatment) within the last 2 weeks before Visit 3. 14. Participants or parent/guardian/caregiver unable to demonstrate correct administration of the investigational product at Visit 1. 15. Concomitant disease other than PAR which could have interfered with the study procedures or outcomes as determined by the investigator. 16. History of hospitalization due to asthma within 1 year before screening (Visit 1). 17. Abnormal 24-hour urinary free cortisol level assessed at screening (Visit 2). The above information was not intended to contain all considerations relevant to potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Growth Velocity | Day 1 to end of treatment (Day 360) | Individual participant's growth velocity over double-blind treatment period was calculated using a linear regression of height over time. Height was measured on the same wall-mounted Harpenden stadiometer with the participant barefoot and in light clothing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment) | PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale: * 0 = symptom absent * 1 = mild (present but not annoying to self) * 2 = moderate (annoying to self but not interfering with sleep or daily living) * 3 = severe (interfered with daily living and/or sleep) Individual symptom scores ranged from 0 (best outcome) to 3 (worst outcome). A negative value for change represents an improvement in symptoms. |
| Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 120, Day 240 and Day 360 | Global efficacy was assessed by the participant (with the help of a parent/guardian/caregiver) using the following scale: * 0 = no relief (symptoms unchanged or worse than before) * 1 = slight relief (symptoms were present and only minimally improved) * 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved) * 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome) * 4 = complete relief (virtually no symptom present) |
| Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 120, Day 240 and Day 360 | Global efficacy was assessed by the investigator using the following scale: * 0 = no relief (symptoms unchanged or worse than before) * 1 = slight relief (symptoms were present and only minimally improved) * 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved) * 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome) * 4 = complete relief (virtually no symptom present) |
| Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study | Baseline (4-6 months before Day 1), double-blind treatment period (Day 1 to Day 360) and follow-up (Day 361 to Day 420) | Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary. The percentage of participants who used the rescue medication during each of the study periods is reported. |
| Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS) | For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment) | PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale: * 0 = symptom absent * 1 = mild (present but not annoying to self) * 2 = moderate (annoying to self but not interfering with sleep or daily living) * 3 = severe (interfered with daily living and/or sleep) TNSS was the sum of the individual symptom scores (ranging 0-3), and TNSS ranged from 0 (best outcome) to 12 (worst outcome). A negative value for change represents an improvement in symptoms. |
| 24 Hour Urinary Free Cortisol Levels | Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420) | Urine cortisol levels was determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be \[1.4 - 21 μg/24 hours\]. |
| 24 Hour Cortisol/Creatinine Ratio | Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420) | Urine cortisol and creatinine levels were determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be \[1.4 - 21 μg/24 hours\]. No normal range is available for cortisol/creatinine ratio. |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | From Day 1 to 7 days following end of treatment (Day 360) | Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind investigational product (IP) are defined as TEAEs. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: * Resulted in death * Was life-threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect * Was a medically important event |
| Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study | double-blind treatment period (Day 1 to Day 360) | Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary. The percentage of days that participants used the rescue medication during the double-blind treatment phase of the study. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between 14 March 2007 (first subject enrolled) and 12 October 2011 (last subject last visit) at 69 active centers located in the US.
Pre-assignment details
299 participants were randomized, 298 were treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 3 to 9 year old participants with PAR administered
* Placebo (once to demonstrate IP administration in the baseline/screening period)
* Placebo in the double-blind treatment period
All participants were provided Children's Claritin® Syrup as a rescue medication | 148 |
| TAA-AQ 3 to 9 year old participants with PAR administered
* Placebo (once to demonstrate IP administration in the baseline/screening period)
* TAA-AQ in the double-blind treatment period
All participants were provided Children's Claritin® Syrup as a rescue medication | 151 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Excluded medication | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 5 | 7 |
| Overall Study | Non-compliance | 2 | 5 |
| Overall Study | Not treated | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 14 | 12 |
| Overall Study | Relocation | 3 | 2 |
| Overall Study | Sponsor decision | 1 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 8 |
Baseline characteristics
| Characteristic | Placebo | TAA-AQ | Total |
|---|---|---|---|
| Age Continuous | 6.24 years STANDARD_DEVIATION 1.55 | 6.12 years STANDARD_DEVIATION 1.62 | 6.18 years STANDARD_DEVIATION 1.58 |
| Age, Customized <=3 to <6 years | 64 participants | 65 participants | 129 participants |
| Age, Customized <=6 to <10 years | 84 participants | 86 participants | 170 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian/Oriental | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Black | 22 participants | 28 participants | 50 participants |
| Race/Ethnicity, Customized Caucasian/White | 114 participants | 111 participants | 225 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 23 participants | 33 participants | 56 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Island | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 125 participants | 118 participants | 243 participants |
| Race/Ethnicity, Customized Other | 8 participants | 10 participants | 18 participants |
| Sex/Gender, Customized Female | 62 participants | 64 participants | 126 participants |
| Sex/Gender, Customized Male | 86 participants | 87 participants | 173 participants |
| Tanner classification at randomization Stage 1 | 148 participants | 151 participants | 299 participants |
| Tanner classification at randomization Stage 2 | 0 participants | 0 participants | 0 participants |
| Tanner classification at randomization Stage 3 | 0 participants | 0 participants | 0 participants |
| Tanner classification at randomization Stage 4 | 0 participants | 0 participants | 0 participants |
| Tanner classification at randomization Stage 5 | 0 participants | 0 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 147 | 109 / 146 |
| serious Total, serious adverse events | 0 / 147 | 2 / 146 |
Outcome results
Primary
Growth Velocity
Individual participant's growth velocity over double-blind treatment period was calculated using a linear regression of height over time. Height was measured on the same wall-mounted Harpenden stadiometer with the participant barefoot and in light clothing.
Time frame: Day 1 to end of treatment (Day 360)
Population: The modified intent-to-treat (mITT) population included all intent-to-treat participants who had at least 3 postrandomization visits with recorded height measurements during the double-blind treatment period, excluding those from Good Clinical Practice (GCP) noncompliant sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Growth Velocity | 6.09 cm/year | Standard Error 0.122 |
| TAA-AQ | Growth Velocity | 5.65 cm/year | Standard Error 0.122 |
p-value: 0.009695% CI: [-0.78, -0.11]ANCOVA
Secondary
24 Hour Cortisol/Creatinine Ratio
Urine cortisol and creatinine levels were determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be \[1.4 - 21 μg/24 hours\]. No normal range is available for cortisol/creatinine ratio.
Time frame: Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420)
Population: All randomized and treated participants, excluding those from GCP noncompliant sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 24 Hour Cortisol/Creatinine Ratio | at baseline (N=145, N=141) | 18.94 μg/g Creatinine | Standard Deviation 9.64 |
| Placebo | 24 Hour Cortisol/Creatinine Ratio | at end of treatment (N=114, N=118) | 15.47 μg/g Creatinine | Standard Deviation 12.6 |
| Placebo | 24 Hour Cortisol/Creatinine Ratio | at follow-up (N=96, N=97) | 17.01 μg/g Creatinine | Standard Deviation 12.63 |
| TAA-AQ | 24 Hour Cortisol/Creatinine Ratio | at follow-up (N=96, N=97) | 15.10 μg/g Creatinine | Standard Deviation 9.54 |
| TAA-AQ | 24 Hour Cortisol/Creatinine Ratio | at baseline (N=145, N=141) | 19.44 μg/g Creatinine | Standard Deviation 10.62 |
| TAA-AQ | 24 Hour Cortisol/Creatinine Ratio | at end of treatment (N=114, N=118) | 15.86 μg/g Creatinine | Standard Deviation 10.77 |
Secondary
24 Hour Urinary Free Cortisol Levels
Urine cortisol levels was determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be \[1.4 - 21 μg/24 hours\].
Time frame: Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420)
Population: All randomized and treated participants, excluding those from GCP noncompliant sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 24 Hour Urinary Free Cortisol Levels | at baseline (N=146, N=141) | 7.44 μg/24 hours | Standard Deviation 4.23 |
| Placebo | 24 Hour Urinary Free Cortisol Levels | at end of treatment (EOT) (N=114, N=118) | 7.05 μg/24 hours | Standard Deviation 5.33 |
| Placebo | 24 Hour Urinary Free Cortisol Levels | at follow-up (N=96, N=97) | 7.85 μg/24 hours | Standard Deviation 5.65 |
| TAA-AQ | 24 Hour Urinary Free Cortisol Levels | at baseline (N=146, N=141) | 7.44 μg/24 hours | Standard Deviation 4.04 |
| TAA-AQ | 24 Hour Urinary Free Cortisol Levels | at end of treatment (EOT) (N=114, N=118) | 7.42 μg/24 hours | Standard Deviation 5.93 |
| TAA-AQ | 24 Hour Urinary Free Cortisol Levels | at follow-up (N=96, N=97) | 7.00 μg/24 hours | Standard Deviation 5.28 |
Secondary
Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment
PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale: * 0 = symptom absent * 1 = mild (present but not annoying to self) * 2 = moderate (annoying to self but not interfering with sleep or daily living) * 3 = severe (interfered with daily living and/or sleep) Individual symptom scores ranged from 0 (best outcome) to 3 (worst outcome). A negative value for change represents an improvement in symptoms.
Time frame: For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment)
Population: mITT population with available nasal symptom scores: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period with available nasal symptom scores, excluding those from GCP noncompliant sites.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Nasal stuffiness (N=101, N=104) | -0.68 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Nasal discharge (N=102, N=103) | -0.67 score on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Sneezing (N=102, N=103) | -0.64 score on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Nasal Itching (N=101, N=104) | -0.69 score on a scale | Standard Error 0.08 |
| TAA-AQ | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Nasal Itching (N=101, N=104) | -0.71 score on a scale | Standard Error 0.08 |
| TAA-AQ | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Nasal stuffiness (N=101, N=104) | -0.83 score on a scale | Standard Error 0.08 |
| TAA-AQ | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Sneezing (N=102, N=103) | -0.55 score on a scale | Standard Error 0.07 |
| TAA-AQ | Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment | Change in Nasal discharge (N=102, N=103) | -0.71 score on a scale | Standard Error 0.07 |
Comparison: Change in nasal stuffinessp-value: 0.196395% CI: [-0.37, 0.08]ANCOVA
Comparison: Change in Nasal Dischargep-value: 0.719395% CI: [-0.24, 0.17]ANCOVA
Comparison: Change in Sneezingp-value: 0.40295% CI: [-0.12, 0.29]ANCOVA
Comparison: Change in Nasal Itchingp-value: 0.885495% CI: [-0.23, 0.2]ANCOVA
Secondary
Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS)
PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale: * 0 = symptom absent * 1 = mild (present but not annoying to self) * 2 = moderate (annoying to self but not interfering with sleep or daily living) * 3 = severe (interfered with daily living and/or sleep) TNSS was the sum of the individual symptom scores (ranging 0-3), and TNSS ranged from 0 (best outcome) to 12 (worst outcome). A negative value for change represents an improvement in symptoms.
Time frame: For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment)
Population: mITT population with scores available for TNSS: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period with scores available for TNSS, excluding those from GCP noncompliant sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS) | -2.68 score on a scale | Standard Error 0.26 |
| TAA-AQ | Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS) | -2.80 score on a scale | Standard Error 0.25 |
p-value: 0.734195% CI: [-0.83, 0.58]ANCOVA
Secondary
Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period
Global efficacy was assessed by the investigator using the following scale: * 0 = no relief (symptoms unchanged or worse than before) * 1 = slight relief (symptoms were present and only minimally improved) * 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved) * 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome) * 4 = complete relief (virtually no symptom present)
Time frame: Day 120, Day 240 and Day 360
Population: mITT population: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period, excluding those from GCP noncompliant sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 120 (N=128, N=130) | 1.89 score on a scale | Standard Deviation 1.11 |
| Placebo | Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 240 (N=115, N=136) | 2.11 score on a scale | Standard Deviation 1.07 |
| Placebo | Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 360 (N=125, N=125) | 1.80 score on a scale | Standard Deviation 0.98 |
| TAA-AQ | Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 240 (N=115, N=136) | 2.21 score on a scale | Standard Deviation 1.08 |
| TAA-AQ | Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 120 (N=128, N=130) | 2.04 score on a scale | Standard Deviation 1.04 |
| TAA-AQ | Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period | Day 360 (N=125, N=125) | 2.14 score on a scale | Standard Deviation 1.16 |
Comparison: Statistical Analysis for Day 120p-value: 0.2445Mixed model for repeated measures
Comparison: Statistical Analysis for Day 240p-value: 0.4488Mixed model for repeated measures
Comparison: Statistical Analysis for Day 360p-value: 0.0142Mixed model for repeated measures
Secondary
Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period
Global efficacy was assessed by the participant (with the help of a parent/guardian/caregiver) using the following scale: * 0 = no relief (symptoms unchanged or worse than before) * 1 = slight relief (symptoms were present and only minimally improved) * 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved) * 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome) * 4 = complete relief (virtually no symptom present)
Time frame: Day 120, Day 240 and Day 360
Population: mITT population: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period, excluding those from GCP noncompliant sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 120 (N=127, N=131) | 1.87 score on a scale | Standard Deviation 1.1 |
| Placebo | Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 240 (N=115, N=116) | 1.97 score on a scale | Standard Deviation 1.04 |
| Placebo | Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 360 (N=125, N=125) | 1.86 score on a scale | Standard Deviation 1.08 |
| TAA-AQ | Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 120 (N=127, N=131) | 2.09 score on a scale | Standard Deviation 1 |
| TAA-AQ | Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 240 (N=115, N=116) | 2.16 score on a scale | Standard Deviation 1.03 |
| TAA-AQ | Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period | Day 360 (N=125, N=125) | 2.18 score on a scale | Standard Deviation 1.19 |
Comparison: Statistical Analysis for Day 120p-value: 0.0951Mixed model for repeated measures
Comparison: Statistical analysis for Day 240p-value: 0.1247Mixed model for repeated measures
Comparison: Statistical analysis for Day 360p-value: 0.0207Mixed model for repeated measures
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind investigational product (IP) are defined as TEAEs. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: * Resulted in death * Was life-threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect * Was a medically important event
Time frame: From Day 1 to 7 days following end of treatment (Day 360)
Population: All randomized and treated participants, excluding those from GCP noncompliant sites.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any treatment emergent SAE | 0 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any TEAE leading to death | 0 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any TEAE leading to permanent discontinuation | 3 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with investigational product (IP) overdose TEAE | 0 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any TEAE | 113 participants |
| TAA-AQ | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with investigational product (IP) overdose TEAE | 0 participants |
| TAA-AQ | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any TEAE | 117 participants |
| TAA-AQ | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any treatment emergent SAE | 2 participants |
| TAA-AQ | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any TEAE leading to permanent discontinuation | 1 participants |
| TAA-AQ | Number of Participants With Treatment-emergent Adverse Events (TEAE) | with any TEAE leading to death | 0 participants |
Secondary
Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study
Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary. The percentage of days that participants used the rescue medication during the double-blind treatment phase of the study.
Time frame: double-blind treatment period (Day 1 to Day 360)
Population: mITT population: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period, excluding those from GCP noncompliant sites.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study | 20.39 percentage of days | Standard Deviation 28.02 |
| TAA-AQ | Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study | 15.69 percentage of days | Standard Deviation 21.53 |
Secondary
Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study
Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary. The percentage of participants who used the rescue medication during each of the study periods is reported.
Time frame: Baseline (4-6 months before Day 1), double-blind treatment period (Day 1 to Day 360) and follow-up (Day 361 to Day 420)
Population: mITT population: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period, excluding those from GCP noncompliant sites.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study | 81.2 percentage of participants |
| TAA-AQ | Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study | 90.3 percentage of participants |