A Safety and Efficacy Study of Ciclesonide Nasal Aerosol in Subjects 6-11 Years With Perennial Allergic Rhinitis (PAR).

Study Overview
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Brief Summary
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This is a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of ciclesonide nasal aerosol administered once daily to male and premenarchal female subjects 6 to 11 years of age with a diagnosis of PAR.

Detailed Description
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This is a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of ciclesonide nasal aerosol administered once daily to male and premenarchal female subjects 6 to 11 years of age with a diagnosis of PAR. This study will consist of the following periods/visits: Screening , Single-blind Placebo Run-in period, Double-blind Treatment period , Follow-up. The total duration of subject participation will be approximately 5 months.

Official Title
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A 12-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Safety and Efficacy Study of Ciclesonide Nasal Aerosol in Subjects 6-11 Years With Perennial Allergic Rhinitis

Conditions
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Perennial Allergic Rhinitis, PAR

Intervention / Treatment
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* Drug: Ciclesonide nasal aerosol 37 mcg
* Drug: ciclesonide nasal aerosol 74 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gives written informed consent (parent/legal guardian) and assent (from the child), including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation. Is a male or premenarchal female 6 to 11 years old at the screening visit. Is in general good health (defined as the absence of any clinically relevant abnormalities as determined by the investigator) based on screening physical examination and medical history. Has a history of PAR to a relevant perennial allergen (house dust mites, cockroaches, molds, and animal dander) for a minimum of 1 year immediately preceding the study screening visit. The PAR must have been of sufficient severity to have required treatment (either continuous or intermittent) in the past and require treatment throughout the entire study period. Has a demonstrated sensitivity to at least 1 allergen known to induce PAR (house dust mites, cockroaches, molds, and animal dander) based on a documented result with a standard skin-prick test either within 12 months prior to screening visit or performed at the screening visit. A positive test is defined as a wheal diameter at least 3 mm larger than the negative control wheal for the skin-prick test. The subject's positive allergen test must be consistent with the medical history of PAR, and the allergen must be present in the subject's environment throughout the study. Subject or parent/guardian must possess an educational level and degree of understanding of English that enables them to communicate suitably with the Investigator and study coordinator as well as accurately complete both the AR diary and PRQLQ Exclusion Criteria: Has a history of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations; recent unhealed nasal biopsy; nasal trauma; or nasal ulcers or perforations. Surgery and atrophic rhinitis or rhinitis medicamentosa are not permitted within the 120 days prior to the screening visit. Has evidence of infection, significant anatomic abnormality, ulceration of the mucosa, blood in the nose, or any other clinically relevant finding on nasal examination at the screening visit. Has nasal jewelry. Has participated in any investigational drug trial within the 30 days preceding the screening visit or is planning participation in another investigational drug trial at any time during this trial. Has a known hypersensitivity to any corticosteroid or any of the excipients in the formulation of ciclesonide. Has a history of a respiratory infection or disorder, including but not limited to bronchitis, pneumonia, influenza, and severe acute respiratory syndrome, within the 14 days preceding the screening visit. Has active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta-agonists and any controller drugs (eg, theophylline, leukotriene antagonists); intermittent use (≤ 3 uses per week) of inhaled short-acting beta-agonists is acceptable. Use of short-acting beta-agonists for exercise-induced bronchospasm will be allowed. Is expecting to use any disallowed concomitant medications during the treatment period. Is, in the investigator's judgment, having a seasonal exacerbation at the time of the screening visit or is likely to have one during the study. Is planning initiation of immunotherapy during the study period or dose escalation during the study period. However, initiation of immunotherapy 90 days or more prior to the screening visit and use of a stable (maintenance) dose (30 days or more) may be considered for inclusion. Has nonvaccinated exposure to or active infection with chickenpox or measles within the 21 days preceding the screening visit. Initiates pimecrolimus cream 1% or greater or tacrolimus ointment 0.03% or greater during the study period or plans a dose escalation during the study period. However, initiation of these creams/ointments 30 days or more prior to screening and use of a stable (maintenance) dose during the study period may be considered for inclusion. Is a child or relative of any clinical investigator or site personnel, even those who are not directly involved in this study. Resides in the same household as another subject who is participating in this study. Has any of the following conditions that are judged by the investigator to be clinically significant and/or to affect the subject's ability to participate in the clinical trial: impaired hepatic function history of ocular disturbances, eg, glaucoma or posterior subcapsular cataracts or herpes simplex any systemic infection hematological (including anemia), hepatic, renal, endocrine disease gastrointestinal disease malignancy (excluding basal cell carcinoma) current neuropsychological condition with or without drug therapy. Any behavioral condition that could affect the subject's ability to accurately report symptoms to the caregiver such as developmental delay, attention deficit disorder, and autism. Has any condition that, in the judgment of the investigator, would preclude the subject from completing the protocol with the capture of the assessments as written. Has received ciclesonide nasal aerosol in a previous clinical trial.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ciclesonide nasal aerosol 37mcg<br>ciclesonide nasal aerosol 37mcg - the dose is administered as 1 actuation per nostril to give a total dose of 37mcg once daily | Drug: Ciclesonide nasal aerosol 37 mcg<br>* ciclesonide nasal aerosol 37mcg - the dose is administered as 1 actuation per nostril to give a total dose of 37<br>|
| Active Comparator: ciclesonide nasal aerosol 74 mcg<br>ciclesonide nasal aerosol 74 mcg - the dose is administered as 1 actuation per nostril to give a total dose of 74 mcg once daily | Drug: ciclesonide nasal aerosol 74 mcg<br>* ciclesonide nasal aerosol 74 mcg - the dose is administered as 1 actuation per nostril to give a total dose of 74 mcg<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo - one dose per nostril<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in Average Daily Subject-reported AM and PM Reflective Total Nasal Symptom Scores (rTNSS) Averaged Weekly Over the First 6 Weeks of the Double-blind Treatment. | TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement. | Weeks 0-6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Daily Subject-reported AM and PM Instantaneous Total Nasal Symptom Scores (iTNSS) Averaged Weekly Over the First 6 Weeks of Double-blind Treatment | TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement. | Weeks 0 -6 | 
| Change From Baseline in the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Overall Score at the End of the First 6 Weeks of Double-blind Treatment | PRQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with rhinoconjunctivitis. The PRQLQ has 23 questions in 5 domains (nose symptoms, eye symptoms, practical problems, activity limitation, and other symptoms). Children recalled how they were during the previous week and responded to each question on a 7-point scale (0 = not bothered to 6 = extremely bothered or 0 = none of the time to 6 = all of the time) for a total possible score of 138. The overall PRQLQ score is the mean of all 23 responses. | Weeks 0 -6 | 
| Change From Baseline in Daily Average Subject-reported AM and PM rTNSS Averaged Weekly Over the 12-week Double-blind Treatment Period | TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the twelve week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement | Weeks 0 -12 | 
| Change From Baseline in Daily Average Subject-reported AM and PM iTNSS Averaged Weekly Over the 12-week Double-blind Treatment Period | TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the twelve week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement. | Weeks 0 -12 | 
| Change From Baseline in Daily Average Subject-reported AM iTNSS Averaged Over the First 6 Weeks of Double-blind Treatment | TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement. | Weeks 0 -6 | 
| Change From Baseline in Daily PRQLQ Overall Score at the End of the 12-week Double-blind Treatment Period | PRQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with rhinoconjunctivitis. The PRQLQ has 23 questions in 5 domains (nose symptoms, eye symptoms, practical problems, activity limitation, and other symptoms). Children recalled how they were during the previous week and responded to each question on a 7-point scale (0 = not bothered to 6 = extremely bothered or 0 = none of the time to 6 = all of the time) for a total possible score of 138. The overall PRQLQ score is the mean of all 23 responses. | Weeks 0 -12 | 
| Time to Maximal Effect [Time to >= 90% Maximum Difference From Placebo in LS Means (Days)] | The time to maximal effect is defined as the number of days until the first treatment day on which the estimated difference between active ciclesonide nasal aerosol and placebo is at least 90% of the largest estimated difference.This is based on the analyses of change from baseline in the average of AM and PM reflective TNSS scores for each day. The time to achieve at least 90% of these estimated differences was calculated. | Weeks 0 -6 | 
| Number of Subjects Experiencing AEs, SAEs, and Discontinuations Due to AEs |  | Weeks 0 -12 | 
| Percentage of Subjects Experiencing AEs, SAEs, and Discontinuations Due to AEs |  | Weeks 0 -12 | 
| Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation |  | Weeks 0 -12 | 
| Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation |  | Weeks 0 -12 |