A 6 Month Safety and Efficacy Study of Once Daily Ciclesonide Hydrofluoroalkane (HFA) in the Treatment of Perennial Allergic Rhinitis (PAR) in Subjects 12 Years and Older

Study Overview
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Brief Summary
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This is a 6-month multi-center, randomized, double-blind, placebo-controlled, parallel group, efficacy and safety study of ciclesonide HFA nasal aerosol administered once-daily to male and female subjects 12 years or older diagnosed with perennial allergic rhinitis (PAR).

Detailed Description
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This study will investigate the efficacy and safety of once daily ciclesonide HFA Nasal Aerosol for 26 weeks. The primary objective is to evaluate the efficacy of ciclesonide HFA (80 mcg and 160 mcg) over 6 weeks, compared to placebo in subjects with PAR. Secondary objectives are to evaluate safety and tolerability and quality of life after treatment with ciclesonide HFA (80 mcg and 160 mcg), over 6 weeks and over 6 months. The study will consist of a Screening period (7 to 21 (±3) days) from Visit 1 to Visit 2, followed by a Single-blind Placebo Run-in period (7 to 10 days) from Visit 2 to Visit 3, followed by a 6-month (26 weeks) double-blind treatment period (Visit 3 through Visit 11). Subjects who complete this study will be allowed to participate in a 6-month open-label extension study (Study 060-635). This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Official Title
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A 6-Month Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of Once Daily Ciclesonide HFA Nasal Aerosol (80 and 160 μg) in The Treatment of Perennial Allergic Rhinitis (PAR) in Subjects 12 Years and Older

Conditions
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Allergic Rhinitis, Perennial Allergic Rhinitis

Intervention / Treatment
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* Drug: Ciclesonide HFA 80 mcg
* Drug: Ciclesonide HFA 160 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Give written informed consent and assent, including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation. Subject must be in general good health based on screening physical examination, medical history, and clinical laboratory values. If any of the Screening visit Hematology, Chemistries, or Urinalysis are not within the clinical laboratory's reference range, then the subject can be included only if the Investigator judges the deviations to be not clinically significant. A history of PAR to a relevant perennial allergen (house dust mites, cockroach, molds, animal dander) for a minimum of two years 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. A demonstrated sensitivity at the Screening visit to at least one allergen known to induce PAR (house dust mite, animal dander, cockroach, and molds) using a standard skin-prick test. The subject's positive allergen test must be consistent with the medical history of PAR and must be present in the subject's environment throughout the study. Based upon subject's medical history, in the Investigator's judgment, the subject is unlikely to have a seasonal exacerbation during the first 6 weeks of double-blind treatment. Subject, if female ≤65 years of age, must have a negative serum pregnancy test at screening. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control. Exclusion Criteria: Female subject who is pregnant or lactating. History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations; recent nasal biopsy; nasal trauma; or nasal ulcers or perforations. Surgery and atrophic rhinitis or rhinitis medicamentosa are not permitted within the last 60 days prior to the Screening visit. Subject is, in the investigator's judgement, having a seasonal exacerbation at the time of screening. Participation in any investigational drug trial within the 30 days preceding the Screening visit or planned participation in another investigational drug trial at any time during this trial. A known hypersensitivity to any corticosteroid or any of the excipients in the formulation of ciclesonide. History of a respiratory infection or disorder [including, but not limited to bronchitis, pneumonia, influenza, severe acute respiratory syndrome (SARS)] within the 14 days preceding the Screening visit. History of alcohol or drug abuse within 2 years preceding the Screening visit . History of a positive test for HIV, hepatitis B or hepatitis C. Active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta agonists and any controller drugs (eg, theophylline, leukotriene antagonists, etc.); intermittent use (less than or equal to 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. Expected use of any disallowed concomitant medications during the treatment period. 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. Previous participation in an intranasal ciclesonide HFA nasal aerosol study. Non-vaccinated exposure to or active infection with, chickenpox or measles within the 21 days preceding the Screening Visit. Initiation of pimecrolimus cream 1% or greater or tacrolimus ointment 0.03% or greater during the study period or planned dose escalation during the study period. Study participation by clinical investigator site employees and/or their immediate relatives who reside in the same household. Study participation by more than one subject from the same household. 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: impaired hepatic function including alcohol related liver disease or cirrhosis history of ocular disturbances, eg, glaucoma or posterior subcapsular cataracts any systemic infection hematological, hepatic, renal, endocrine (except for controlled diabetes mellitus or postmenopausal symptoms or hypothyroidism) gastrointestinal disease malignancy (excluding basal cell carcinoma) current neuropsychological condition with or without drug therapy • Any condition that, in the judgment of the investigator, would preclude the subject from completing the protocol with capture of the assessments as written.

Ages Eligible for Study
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Minimum Age: 12 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 |
| --- | --- |
| Experimental: Ciclesonide HFA 80 mcg once daily<br>Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day). | Drug: Ciclesonide HFA 80 mcg<br>* Ciclesonide HFA Nasal Aerosol 80 mcg once daily for 6 months in the treatment of Perennial Allergic Rhinitis (PAR) in subjects 12 years and older.<br>|
| Experimental: Ciclesonide HFA 160 mcg once daily<br>Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day). | Drug: Ciclesonide HFA 160 mcg<br>* Ciclesonide HFA Nasal Aerosol 160 mcg once daily for 6 months in the treatment of Perennial Allergic Rhinitis (PAR) in subjects 12 years and older.<br>|
| Placebo Comparator: Placebo once daily<br>The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide. | Drug: Placebo<br>* Placebo HFA Nasal Aerosol once daily for 6 months in the treatment of Perennial Allergic Rhinitis (PAR) in subjects 12 years and older.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Daily Subject-reported AM and PM Reflective TNSS (rTNSS) 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 = mild = moderate = 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 Daily Subject-reported AM and PM Instantaneous TNSS (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 = mild = moderate = 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 Subject-reported AM rTNSS 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 = mild = moderate = 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 | 
| Change From Baseline in Daily Subject-reported PM rTNSS 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 = mild = moderate = 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 | 
| Change From Baseline in Daily 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 = mild = moderate = 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 Subject-reported PM 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 = mild = moderate = 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 Subject-reported AM rNSS Averaged Over the First 6 Weeks of the Double-blind Treatment | NSS is the assessment of the 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 = mild = moderate = severe Reflective NSS 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 | 
| Change From Baseline in Daily Subject-reported PM rNSS Averaged Over the First 6 Weeks of the Double-blind Treatment | NSS is the assessment of the 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 = mild = moderate = severe Reflective NSS 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 | 
| Change From Baseline in Daily Subject-reported AM & PM rNSS Averaged Over the First 6 Weeks of Double-blind Treatment Period. | NSS is the assessment of the 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 = mild = moderate = severe Reflective NSS 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 | 
| Change From Baseline in Daily Subject-reported AM iNSS Averaged the First 6 Weeks of the Double-blind Treatment | NSS is the assessment of the 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 = mild = moderate = severe Instantaneous NSS 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 Subject-reported PM iNSS Averaged the First 6 Weeks of the Double-blind Treatment | NSS is the assessment of the 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 = mild = moderate = severe Instantaneous NSS 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 Subject-reported AM and PM iNSS Averaged Over the First 6 Weeks of Double-blind Treatment Period | NSS is the assessment of the 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 = mild = moderate = severe Instantaneous NSS 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 to Week 6 in Rhinoconjunctivitis Quality of Life Questionnaire With Standardized [RQLQ(S)] Overall Score in Impaired Patients With Baseline RQLQ(S) Score ≥3.0 | RQLQ(S) scores in subjects with baseline RQLQ[S] score ≥3.0. RQLQ(S) consists of 28 questions, each question measured on a scale of 0-6 where a higher score indicates poor quality of life. Domains: Activities (questions 1-3), Sleep (questions 4-6), Non-Nose/Eye Symptoms (questions 7-13), Practical Problems (questions 14-16), Nasal Symptoms (questions 17-20), Eye Symptoms (questions 21-24), and Emotional (questions 25-28). The overall RQLQ(S) score was calculated as the average of the mean domain scores. | Baseline and Week 6 | 
| Change From Baseline to Month 6 (Week 26) in RQLQ(S) Overall Score in Impaired Patients With Baseline RQLQ(S) Score ≥3.0. | RQLQ(S) scores in impaired subjects with baseline RQLQ[S] score ≥3.0. RQLQ(S)consists of 28 questions, each question measured on a scale of 0-6 where a higher score indicates poor quality of life. Domains: Activities (questions 1-3), Sleep (questions 4-6), Non-Nose/Eye Symptoms (questions 7-13), Practical Problems (questions 14-16), Nasal Symptoms (questions 17-20), Eye Symptoms (questions 21-24), and Emotional (questions 25-28). The overall RQLQ(S) score was calculated as the average of the mean domain scores. | Baseline and Week 26 |