Study of the Effects of Ciclesonide Hydrofluoroalkane (HFA) Nasal Aerosol on Hypothalamic-Pituitary-Adrenal (HPA) Axis

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01033825
• Collaborator: (none)
• Enrollment: 310
• Locations: 6
• Arms: 7
• Duration (Months): 3.9
• Patients Per Site: 51.7
• Patients Per Site Per Month: 13.1

Study Details

Study Description

Brief Summary

To demonstrate the effects of ciclesonide applied as a nasal aerosol and ciclesonide aqueous (AQ) nasal spray on hypothalamic-pituitary-adrenal axis.

Condition or Disease	Intervention/Treatment	Phase
Perennial Allergic Rhinitis	Drug: Ciclesonide HFA Nasal Aerosol 320 mcg; Drug: Ciclesonide HFA Nasal Aerosol 160 mcg; Drug: HFA Nasal Aerosol placebo; Drug: Ciclesonide Aqueous Nasal Spray 200 mcg; Drug: AQ Nasal Spray Placebo; Drug: Placebo plus Dexamethasone HFA; Drug: Placebo AQ plus Dexamethasone 6 mg	Phase 3

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, safety and efficacy study of the effects of ciclesonide HFA nasal aerosol and ciclesonide AQ nasal spray on the HPA axis, when administered once daily to male and female subjects 12 years or older diagnosed with Perennial Allergic Rhinitis (PAR). The study consists of a screening period, a single blind run in period, a 6 week double blind treatment period including an active control segment, and a follow up period.

Placebo was used as the control during the double-blind treatment period for both delivery methods (HFA nasal aerosol and aqueous nasal spray)and for the study outcome analyses. There was also a positive control administered to a subset of these placebo subjects during the last 4 days of Week 6 (dexamethasone placebo or dexamethasone 6 mg). The active control was utilized to validate the assay sensitivity (ie, distinguish an effective from an ineffective drug) of this study, as dexamethasone is a known HPA axis suppressant, therefore this subset of placebo subjects was not included in the study outcome analyses.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 6-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Safety and Efficacy Study of the Potential Inhibitory Effects on the Hypothalamic-Pituitary-Adrenal Axis of Ciclesonide HFA Nasal Aerosol and Ciclesonide Aqueous Nasal Spray in Subjects 12 Years and Older With Perennial Allergic Rhinitis
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ciclesonide HFA Nasal Aerosol 320 mcg Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Drug: Ciclesonide HFA Nasal Aerosol 320 mcg; Ciclesonide HFA Nasal Aerosol 320 μg once daily
Experimental: Ciclesonide HFA Nasal Aerosol 160 mcg Ciclesonide HFA Nasal Aerosol 160 mcg once daily	Drug: Ciclesonide HFA Nasal Aerosol 160 mcg; Ciclesonide HFA Nasal Aerosol 160 μg once daily
Placebo Comparator: HFA Nasal Aerosol placebo HFA Nasal Aerosol Placebo once daily	Drug: HFA Nasal Aerosol placebo; HFA Nasal Aerosol placebo once daily
Experimental: Ciclesonide Aqueous Nasal Spray 200 mcg Ciclesonide Aqueous Nasal Spray 200 mcg once daily	Drug: Ciclesonide Aqueous Nasal Spray 200 mcg; Ciclesonide Aqueous Nasal Spray 200 mcg once daily; Other Names: Omnaris
Placebo Comparator: AQ Nasal Spray Placebo AQ Nasal Spray Placebo once daily	Drug: AQ Nasal Spray Placebo; AQ Nasal Spray Placebo once daily
Active Comparator: Placebo HFA plus Dexamethasone 6 mcg Placebo HFA plus Dexamethasone 6 mg once daily	Drug: Placebo plus Dexamethasone HFA; Dexamethasone capsules 6 mg once daily; Other Names: Decadron
Active Comparator: Placebo AQ plus Dexamethasone 6 mg Placebo AQ plus Dexamethasone 6 mg once daily	Drug: Placebo AQ plus Dexamethasone 6 mg; Placebo AQ plus Dexamethasone 6 mcg capsules once daily

Outcome Measures

Primary Outcome Measures

1. Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) at Baseline [Baseline]

   AUC(0-24h) will be computed using the linear trapezoidal rule based on the actual time of serum cortisol drawing. AUC(0-24) is then approximated by the sum of the areas of trapezoids. The trapezoid for each time interval is based on the actual times of non-missing cortisol values, and is defined by the actual time interval as the base, the line connecting the two cortisol values, and the two vertical sides at the two time points. Raw data is presented for baseline values (i.e. mean/SD), while inferential statistics are presented for week 6 values (i.e. LS mean/SE).

2. The Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) From Baseline to Week 6 of the Double Blind Treatment Period [week 6]

   Change is calculated as week 6 minus baseline. AUC(0-24h) will be computed using the linear trapezoidal rule based on the actual time of serum cortisol drawing. AUC(0-24) is then approximated by the sum of the areas of trapezoids. The trapezoid for each time interval is based on the actual times of non-missing cortisol values, and is defined by the actual time interval as the base, the line connecting the two cortisol values, and the two vertical sides at the two time points. Raw data is presented for baseline values (i.e. mean/SD), while inferential statistics are presented for week 6 values (i.e. LS mean/SE).

Secondary Outcome Measures

1. Number of Subjects Experiencing Adverse Events (AEs) [Weeks 0-6]

2. Percentage of Subjects Experiencing Adverse Events (AEs) [Weeks 0-6]

3. Number of Subjects Experiencing Serious Adverse Events (SAEs). [Weeks 0-6]

4. Percentage of Subjects Experiencing Serious Adverse Events (SAEs). [Weeks 0-6]

5. Number of Subjects Who Discontinue Due to AEs [Weeks 0-6]

6. Percentage of Subjects Who Discontinue Due to AEs [Weeks 0-6]

7. Number of Subjects Experiencing Local Nasal AEs [Weeks 0-6]

   Local Nasal adverse events are defined as adverse events occurring in the middle ear, nose, throat, and upper respiratory tract down to the larynx, anatomic regions.

8. Percentage of Subjects Experiencing Local Nasal AEs [Weeks 0-6]

   Local Nasal adverse events are defined as adverse events occurring in the middle ear, nose, throat, and upper respiratory tract down to the larynx, anatomic regions.

9. Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-12h) at Baseline [Baseline]

10. Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-12h) From Baseline After 6 Weeks of Treatment [Weeks 0-6]

11. Serum Cortisol Area Under the Concentration-time Curve (AUC)(12-24h) at Baseline [Baseline]

12. Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(12-24h) From Baseline After 6 Weeks of Treatment [Weeks 0-6]

13. Baseline Daily Subject-reported AM Reflective TNSS [Baseline]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

14. Change From Baseline in Daily Subject-reported AM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

15. Baseline Daily Subject-reported PM Reflective TNSS [Baseline]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

16. Change From Baseline in Daily Subject-reported PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

17. Baseline Daily Subject-reported AM Instantaneous TNSS [Baseline]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

18. Change From Baseline in Daily Subject-reported AM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

19. Baseline Daily Subject-reported AM and PM Reflective TNSS [Baseline]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

20. Change From Baseline in Daily Subject-reported AM and PM Reflective TNSS Averaged Over Each Week, and Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

21. Baseline Daily Subject-reported PM Instantaneous TNSS [Baseline]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

22. Change From Baseline in Daily Subject-reported PM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

23. Baseline Daily Subject-reported AM and PM Instantaneous TNSS [Baseline]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

24. Change From Baseline in Daily Subject-reported AM and PM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.

25. Baseline Daily Subject-reported Individual AM Reflective NSS [Baseline]

    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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

26. Change From Baseline in Daily Subject-reported Individual AM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period [Weeks 0-6]

    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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

27. Baseline Daily Subject-reported Individual PM Reflective NSS [Baseline]

    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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

28. Change From Baseline in Daily Subject-reported Individual PM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period [Weeks 0-6]

    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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

29. Baseline Daily Subject-reported Individual AM and PM Reflective NSS [Baseline]

    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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

30. Change From Baseline in Daily Subject-reported Individual AM and PM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period [Weeks 0-6]

    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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

31. Baseline Daily Subject-reported Individual AM Instantaneous NSS [Baseline]

    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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

32. Change From Baseline in Daily Subject-reported Individual AM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

33. Baseline Daily Subject-reported Individual PM Instantaneous NSS [Baseline]

    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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

34. Change From Baseline in Daily Subject-reported Individual PM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

35. Baseline Daily Subject-reported Individual AM and PM Instantaneous NSS [Baseline]

    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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

36. Change From Baseline in Daily Subject-reported Individual AM and PM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment [Weeks 0-6]

    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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.

37. Time to Maximal Effect Over 6 Weeks of Double-blind Treatment. [Weeks 0-6]

    The time to maximal effect is defined as the number of days until the first treatment day on which the estimated difference between each active treatment group and corresponding 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 evaluation is made separately for each dose level of Ciclesonide HFA compared to placebo. Difference is calculated as placebo - ciclesonide. Analysis of HFA data and AQ data were conducted separately.

38. Ratio (Percentage) of Correct Advances of the Dose Indicator Out of Expected Advances. [Weeks 1-2, 2-4]

    Ratio of correct advance is defined as the (number of doses actuated/number of dose reported).

39. Number of Devices With Actuation Consistency [Weeks 1-4]

    Actuation consistency is defined as a dose indicator count within ±20% of the subject self report of study medication administration.

40. Percentage of Devices With Actuation Consistency [Weeks 1-4]

    Actuation consistency is defined as a dose indicator count within ±20% of the subject self report of study medication administration.

41. Number of Devices With Major Discrepancies [Week 6]

    A major discrepancy is defined as a discrepancy of >20 actuations between the dose indicator and subject self report of study medication administration.

42. Percentage of Devices With Major Discrepancies [Week 6]

    A major discrepancy is defined as a discrepancy of >20 actuations between the dose indicator and subject self report of study medication administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 (defined as the absence of any clinically relevant abnormalities as determined by the Investigator) based on screening physical examination, medical history, and clinical laboratory values (Hematology, Chemistries and Urinalysis).

• If any of the screening 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 to at least one allergen known to induce PAR (house dust mite, animal dander, cockroach, and molds) based on a documented result with a standard skin-prick test either within 90 days prior to screening 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 must be present in the subject's environment throughout the study.

• Subject, if female, 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.

1. An oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 1 month prior to entering the study with continued use throughout the study and for thirty days following study participation.

2. Barrier method of contraception, eg, condom and/or diaphragm with spermicide while participating in the study.

3. Abstinence.

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 120 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 randomization 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. 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.

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
2	Northeast Medical Research Associates	North Dartmouth	Massachusetts	United States	02747
3	Clinical Research Institute	Minneappolis	Minnesota	United States	55402
4	Princeton Center for Clinical Research	Skillman	New Jersey	United States	08558
5	Central Texas Health Research	New Braunfels	Texas	United States	78130
6	Sylvana Research	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Sunovion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT01033825
• Other Study ID Numbers: 060-610
• First Posted: Dec 17, 2009
• Last Update Posted: Jul 19, 2012
• Last Verified: Jul 1, 2012

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Ciclesonide; Dexamethasone; Dexamethasone acetate; BB 1101

Study Results

Participant Flow

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo	Placebo HFA Plus Dexamethasone 6 mg	Placebo AQ Plus Dexamethasone 6 mg
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily	Placebo HFA plus Dexamethasone 6 mg once daily. Placebo is the study control & used for the study outcome analyses (CIC placebo/DEX placebo) for each delivery method (HFA or AQ). The positive control was used in a subset of the placebo subjects (18 subjects) during the last 4 days of Week 6. The active control was utilized to validate the assay sensitivity of the study, therefore this subset of placebo subjects was not included in the study outcome analyses.	Placebo AQ plus Dexamethasone 6 mg once daily. Placebo is the study control & used for the study outcome analyses (CIC placebo/DEX placebo) for each delivery method (HFA or AQ). The positive control was used in a subset of these placebo subjects (18 subjects) during the last 4 days of Week 6. The active control was utilized to validate the assay sensitivity of the study, therefore this subset of placebo subjects was not included in the study outcome analyses.
Period Title: Overall Study
STARTED	51	60	57	48	58	18	18
COMPLETED	48	57	55	46	56	18	18
NOT COMPLETED	3	3	2	2	2	0	0

Baseline Characteristics

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo	Placebo HFA Plus Dexamethasone 6 mg	Placebo AQ Plus Dexamethasone 6 mg	Total
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily	Placebo HFA plus Dexamethasone 6 mg once daily. Placebo is the study control & used for the study outcome analyses (CIC placebo/DEX placebo) for each delivery method (HFA or AQ). The positive control was used in a subset of the placebo subjects (18 subjects) during the last 4 days of Week 6. The active control was utilized to validate the assay sensitivity of the study, therefore this subset of placebo subjects was not included in the study outcome analyses.	Placebo AQ plus Dexamethasone 6 mg once daily. Placebo is the study control & used for the study outcome analyses (CIC placebo/DEX placebo) for each delivery method (HFA or AQ). The positive control was used in a subset of these placebo subjects (18 subjects) during the last 4 days of Week 6. The active control was utilized to validate the assay sensitivity of the study, therefore this subset of placebo subjects was not included in the study outcome analyses.	Total of all reporting groups
Overall Participants	51	60	57	48	58	18	18	310
Age (Count of Participants)
<=18 years	4 7.8%	10 16.7%	12 21.1%	8 16.7%	9 15.5%	2 11.1%	3 16.7%	48 15.5%
Between 18 and 65 years	47 92.2%	50 83.3%	43 75.4%	40 83.3%	48 82.8%	16 88.9%	15 83.3%	259 83.5%
>=65 years	0 0%	0 0%	2 3.5%	0 0%	1 1.7%	0 0%	0 0%	3 1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.8 (13.62)	34.5 (13.42)	33.0 (15.69)	32.3 (12.53)	35.5 (14.55)	35.4 (12.94)	34.0 (134.41)	34.26 (14.01)
Sex: Female, Male (Count of Participants)
Female	32 62.7%	37 61.7%	37 64.9%	30 62.5%	33 56.9%	6 33.3%	12 66.7%	187 60.3%
Male	19 37.3%	23 38.3%	20 35.1%	18 37.5%	25 43.1%	12 66.7%	6 33.3%	123 39.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 21.6%	16 26.7%	6 10.5%	11 22.9%	10 17.2%	3 16.7%	3 16.7%	60 19.4%
Not Hispanic or Latino	40 78.4%	44 73.3%	51 89.5%	37 77.1%	48 82.8%	15 83.3%	15 83.3%	250 80.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, customized (particpants) [Number]
White/Caucasian	49	51	52	42	52	15	15	276
Black or African American	1	4	5	4	5	2	1	22
Asian	1	5	0	0	0	0	0	6
American Indian or Alaska Native	0	0	0	1	1	0	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Other	0	0	0	0	0	0	1	1
Multiple	0	0	0	1	0	1	1	3

Outcome Measures

1. Primary Outcome

Title	Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) at Baseline
Description	AUC(0-24h) will be computed using the linear trapezoidal rule based on the actual time of serum cortisol drawing. AUC(0-24) is then approximated by the sum of the areas of trapezoids. The trapezoid for each time interval is based on the actual times of non-missing cortisol values, and is defined by the actual time interval as the base, the line connecting the two cortisol values, and the two vertical sides at the two time points. Raw data is presented for baseline values (i.e. mean/SD), while inferential statistics are presented for week 6 values (i.e. LS mean/SE).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	Placebo Aqueous Nasal Spray
Arm/Group Description	Ciclesonide hydrofluoroalkane (HFA) Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous (AQ) Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	60	57	48	58
Mean (Standard Deviation) [mcg•h/dL]	183.2 (61.9)	171.7 (40.1)	173.1 (53.5)	172.8 (42.5)	179.0 (37.9)

2. Secondary Outcome

Title	Number of Subjects Experiencing Adverse Events (AEs)
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	Placebo Aqueous Nasal Spray
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	75	48	76
Number [participants]	23 45.1%	17 28.3%	23 40.4%	19 39.6%	29 50%

3. Secondary Outcome

Title	Percentage of Subjects Experiencing Adverse Events (AEs)
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	75	48	76
Number [percentage of subjects]	45.1	28.3	30.7	39.6	38.2

4. Secondary Outcome

Title	Number of Subjects Experiencing Serious Adverse Events (SAEs).
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	48	57	75	47	76
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Subjects Experiencing Serious Adverse Events (SAEs).
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	48	57	75	47	76
Number [percentage of subjects]	0	0	0	0	0

6. Secondary Outcome

Title	Number of Subjects Who Discontinue Due to AEs
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	75	48	76
Number [participants]	0 0%	0 0%	0 0%	1 2.1%	0 0%

7. Secondary Outcome

Title	Percentage of Subjects Who Discontinue Due to AEs
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	48	57	75	47	76
Number [percentage of subjects]	0	0	0	2.1	0

8. Secondary Outcome

Title	Number of Subjects Experiencing Local Nasal AEs
Description	Local Nasal adverse events are defined as adverse events occurring in the middle ear, nose, throat, and upper respiratory tract down to the larynx, anatomic regions.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo	Placebo HFA Plus 6 mg Dexamethasone	Placebo AQ Plus 6 mg Dexamethasone
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily	Placebo HFA plus 6 mg Dexamethasone once daily	Placebo AQ plus 6 mg Dexamethasone once daily
Measure Participants	51	60	57	48	58	18	18
Number [participants]	21 41.2%	11 18.3%	8 14%	16 33.3%	11 19%	5 27.8%	1 5.6%

9. Secondary Outcome

Title	Percentage of Subjects Experiencing Local Nasal AEs
Description	Local Nasal adverse events are defined as adverse events occurring in the middle ear, nose, throat, and upper respiratory tract down to the larynx, anatomic regions.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo	Placebo HFA Plus 6 mg Dexamethasone	Placebo AQ Plus 6 mg Dexamethasone
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily	Placebo HFA plus 6 mg Dexamethasone once daily	Placebo AQ plus 6 mg Dexamethasone once daily
Measure Participants	51	60	57	48	58	18	18
Number [percentage of subjects]	41.2	18.3	14.0	33.3	19.0	27.8	5.6

10. Secondary Outcome

Title	Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-12h) at Baseline
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Mean (Standard Deviation) [mcg•h/dL]	99.8 (38.3)	95.1 (28.5)	92.0 (31.3)	91.9 (25.8)	97.2 (25.0)

11. Secondary Outcome

Title	Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-12h) From Baseline After 6 Weeks of Treatment
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Least Squares Mean (Standard Error) [mcg•h/dL]	-1.0 (3.2)	-1.3 (3.0)	0.5 (3.0)	-5.8 (3.0)	-2.9 (2.7)

12. Secondary Outcome

Title	Serum Cortisol Area Under the Concentration-time Curve (AUC)(12-24h) at Baseline
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Mean (Standard Deviation) [mcg•h/dL]	83.4 (30.2)	76.2 (24.0)	81.1 (28.7)	80.9 (26.8)	81.8 (22.8)

13. Secondary Outcome

Title	Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(12-24h) From Baseline After 6 Weeks of Treatment
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Least Squares Mean (Standard Error) [mcg•h/dL]	-3.9 (2.9)	-2.0 (2.7)	-5.9 (2.7)	-6.1 (3.7)	2.2 (3.4)

14. Secondary Outcome

Title	Baseline Daily Subject-reported AM Reflective TNSS
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Mean (Standard Deviation) [units on a scale]	7.55 (2.39)	8.03 (2.27)	7.81 (2.47)	7.91 (2.50)	7.84 (2.58)

15. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Least Squares Mean (Standard Error) [units on a scale]	-1.80 (0.29)	-1.75 (0.26)	-0.35 (0.27)	-1.18 (0.30)	-0.91 (0.28)

16. Secondary Outcome

Title	Baseline Daily Subject-reported PM Reflective TNSS
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Mean (Standard Deviation) [units on a scale]	7.82 (2.40)	8.39 (2.11)	7.83 (2.52)	8.13 (2.66)	8.16 (2.51)

17. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Least Squares Mean (Standard Error) [units on a scale]	-1.77 (0.30)	-1.88 (0.28)	-0.31 (0.28)	-1.14 (0.29)	-1.19 (0.26)

18. Secondary Outcome

Title	Baseline Daily Subject-reported AM Instantaneous TNSS
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Mean (Standard Deviation) [units on a scale]	6.91 (2.68)	7.63 (2.35)	7.37 (2.68)	7.24 (2.43)	7.19 (2.84)

19. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Least Squares Mean (Standard Error) [units on a scale]	-1.52 (0.27)	-1.62 (0.25)	-0.26 (0.25)	-1.23 (0.29)	-0.60 (0.26)

20. Secondary Outcome

Title	Baseline Daily Subject-reported AM and PM Reflective TNSS
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Mean (Standard Deviation) [units on a scale]	7.68 (2.33)	8.20 (2.14)	7.82 (2.45)	8.01 (2.52)	8.01 (2.49)

21. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM and PM Reflective TNSS Averaged Over Each Week, and Averaged Over the 6 Weeks of Double-blind Treatment
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Least Squares Mean (Standard Error) [units on a scale]	-1.78 (0.29)	-1.82 (0.27)	-0.33 (0.27)	-1.16 (0.29)	-1.06 (0.27)

22. Secondary Outcome

Title	Baseline Daily Subject-reported PM Instantaneous TNSS
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Mean (Standard Deviation) [units on a scale]	6.84 (3.09)	7.60 (2.37)	7.13 (2.75)	7.38 (2.68)	7.44 (2.74)

23. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported PM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Least Squares Mean (Standard Error) [units on a scale]	-1.39 (0.28)	-1.67 (0.26)	-0.10 (0.26)	-1.09 (0.30)	-0.88 (0.28)

24. Secondary Outcome

Title	Baseline Daily Subject-reported AM and PM Instantaneous TNSS
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Mean (Standard Deviation) [units on a scale]	6.87 (2.84)	7.62 (2.29)	7.26 (2.67)	7.30 (2.52)	7.33 (2.74)

25. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM and PM Instantaneous TNSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptom 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.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Least Squares Mean (Standard Error) [units on a scale]	-1.45 (0.27)	-1.67 (0.25)	-0.19 (0.25)	-1.15 (0.29)	-0.75 (0.27)

26. Secondary Outcome

Title	Baseline Daily Subject-reported Individual AM Reflective NSS
Description	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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Baseline Nasal Sneezing	1.56 (0.83)	1.65 (0.88)	1.54 (0.89)	1.42 (0.81)	1.57 (0.93)
Baseline Runny Nose	1.99 (0.68)	2.16 (0.63)	2.15 (0.70)	2.27 (0.71)	2.06 (0.76)
Baseline Nasal Itching	1.71 (0.85)	1.89 (0.75)	1.83 (0.83)	1.85 (0.85)	1.92 (0.83)
Baseline Nasal Congestion	2.30 (0.59)	2.32 (0.57)	2.29 (0.60)	2.36 (0.66)	2.29 (0.62)

27. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported Individual AM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period
Description	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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Nasal Sneezing	-0.41 (0.09)	-0.41 (0.08)	-0.09 (0.08)	-0.28 (0.08)	-0.25 (0.08)
Runny Nose	-0.50 (0.08)	-0.50 (0.08)	-0.17 (0.08)	-0.36 (0.10)	-0.29 (0.09)
Nasal Itching	-0.40 (0.08)	-0.40 (0.08)	-0.05 (0.08)	-0.33 (0.09)	-0.25 (0.08)
Nasal Congestion	-0.49 (0.07)	-0.42 (0.07)	-0.05 (0.07)	-0.20 (0.09)	-0.13 (0.08)

28. Secondary Outcome

Title	Baseline Daily Subject-reported Individual PM Reflective NSS
Description	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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Baseline Nasal Sneezing	1.82 (0.71)	1.87 (0.76)	1.69 (0.81)	1.59 (0.83)	1.74 (0.87)
Baseline Runny Nose	2.03 (0.66)	2.20 (0.58)	2.11 (0.71)	2.30 (0.74)	2.16 (0.73)
Baseline Nasal Itching	1.75 (0.83)	2.02 (0.75)	1.80 (0.82)	1.93 (0.87)	2.00 (0.78)
Baseline Nasal Congestion	2.23 (0.72)	2.30 (0.54)	2.23 (0.67)	2.31 (0.73)	2.25 (0.63)

29. Primary Outcome

Title	The Change in Serum Cortisol Area Under the Concentration-time Curve (AUC)(0-24h) From Baseline to Week 6 of the Double Blind Treatment Period
Description	Change is calculated as week 6 minus baseline. AUC(0-24h) will be computed using the linear trapezoidal rule based on the actual time of serum cortisol drawing. AUC(0-24) is then approximated by the sum of the areas of trapezoids. The trapezoid for each time interval is based on the actual times of non-missing cortisol values, and is defined by the actual time interval as the base, the line connecting the two cortisol values, and the two vertical sides at the two time points. Raw data is presented for baseline values (i.e. mean/SD), while inferential statistics are presented for week 6 values (i.e. LS mean/SE).
Time Frame	week 6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	Placebo Aqueous Nasal Spray
Arm/Group Description	Ciclesonide hydrofluoroalkane (HFA) Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous (AQ) Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	60	57	48	58
Least Squares Mean (Standard Error) [mcg•h/dL]	-4.6 (5.0)	-2.6 (4.6)	-5.0 (4.6)	-11.4 (5.7)	-1.0 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide HFA Nasal Aerosol 320 Mcg, HFA Nasal Aerosol Placebo
	Comments	Standard bioequivalence bounds of a 20% difference based on the clinical judgment was used to determine the delta.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be demonstrated if the 95% CI upper bound for the difference between ciclesonide and placebo with placebo dexamethasone (placebo minus ciclesonide) is <Margin. In order to have 90% power to demonstrate non-inferiority of ciclesonide 320 μg to HFA placebo, 46 evaluable subjects per group are needed using a 1-sided alpha level of 0.025, a standard deviation of 55 μg h/dL, a non-inferiority margin of 38 μh /dL, assuming no true difference exists.
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -13.9 to 13.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Null Hypothesis: the difference in serum cortisol levels between placebo and active (placebo-active)>=38 Alternative Hypothesis: the difference in serum cortisol levels between placebo and active (placebo-active)<38

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide HFA Nasal Aerosol 160 Mcg, HFA Nasal Aerosol Placebo
	Comments	Standard bioequivalence bounds of a 20% difference based on the clinical judgment was used to determine the delta.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be demonstrated if the 95% CI upper bound for the difference between ciclesonide and placebo with placebo dexamethasone (placebo minus ciclesonide) is <Margin. In order to have 90% power to demonstrate non-inferiority of ciclesonide 320 μg to HFA placebo, 46 evaluable subjects per group are needed using a 1-sided alpha level of 0.025, a standard deviation of 55 μg h/dL, a non-inferiority margin of 38 μh /dL, assuming no true difference exists.
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -15.1 to 10.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide Aqueous Nasal Spray 200 Mcg, Placebo Aqueous Nasal Spray
	Comments	Standard bioequivalence bounds of a 20% difference based on the clinical judgment was used to determine the delta.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be demonstrated if the 95% CI upper bound for the difference between ciclesonide and placebo with placebo dexamethasone (placebo minus ciclesonide) is <Margin. In order to have 90% power to demonstrate non-inferiority of ciclesonide nasal spray 200 μg to placebo nasal spray 46 evaluable (per protocol) subjects per group are needed using a 1-sided alpha level of 0.025, a standard deviation of 55 μg h/dL, a non-inferiority margin of 38 μh /dL
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.4
	Confidence Interval	(2-Sided) 95%; -4.7 to 25.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported Individual PM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period
Description	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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Nasal Sneezing	-0.45 (0.09)	-0.48 (0.08)	-0.13 (0.08)	-0.23 (0.08)	-0.27 (0.08)
Runny Nose	-0.49 (0.08)	-0.48 (0.08)	-0.09 (0.08)	-0.37 (0.09)	-0.37 (0.08)
Nasal Itching	-0.38 (0.08)	-0.46 (0.08)	-0.05 (0.08)	-0.32 (0.09)	-0.34 (0.08)
Nasal Congestion	-0.44 (0.08)	-0.44 (0.07)	-0.04 (0.07)	-0.20 (0.09)	-0.21 (0.08)

31. Secondary Outcome

Title	Baseline Daily Subject-reported Individual AM and PM Reflective NSS
Description	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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Baseline Nasal Sneezing	1.69 (0.73)	1.76 (0.79)	1.62 (0.83)	1.51 (0.78)	1.66 (0.87)
Baseline Runny Nose	2.01 (0.65)	2.18 (0.59)	2.13 (0.69)	2.29 (0.70)	2.11 (0.72)
Baseline Nasal Itching	1.73 (0.83)	1.95 (0.73)	1.82 (0.80)	1.89 (0.85)	1.96 (0.79)
Baseline Nasal Congestion	2.26 (0.63)	2.31 (0.53)	2.26 (0.62)	2.33 (0.67)	2.27 (0.61)

32. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported Individual AM and PM Reflective NSS Averaged Over the 6 Weeks of Double-blind Treatment Period
Description	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 (no sign/symptom evident); = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Nasal Sneezing	-0.43 (0.09)	-0.45 (0.08)	-0.11 (0.08)	-0.25 (0.08)	-0.26 (0.07)
Runny Nose	-0.50 (0.08)	-0.50 (0.07)	-0.13 (0.08)	-0.37 (0.09)	-0.33 (0.08)
Nasal Itching	-0.39 (0.08)	-0.43 (0.08)	-0.05 (0.08)	-0.32 (0.09)	-0.30 (0.08)
Nasal Congestion	-0.47 (0.07)	-0.43 (0.07)	-0.04 (0.07)	-0.20 (0.09)	-0.17 (0.08)

33. Secondary Outcome

Title	Baseline Daily Subject-reported Individual AM Instantaneous NSS
Description	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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Baseline Nasal Sneezing	1.24 (0.82)	1.43 (0.96)	1.34 (0.94)	1.15 (0.85)	1.30 (1.02)
Baseline Runny Nose	1.83 (0.84)	2.08 (0.66)	2.01 (0.74)	2.08 (0.68)	1.93 (0.89)
Baseline Nasal Itching	1.61 (0.86)	1.85 (0.75)	1.76 (0.89)	1.76 (0.89)	1.76 (0.91)
Baseline Nasal Congestion	2.24 (0.67)	2.27 (0.58)	2.27 (0.60)	2.25 (0.66)	2.20 (0.66)

34. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported Individual AM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Nasal Sneezing	-0.32 (0.08)	-0.37 (0.07)	-0.06 (0.08)	-0.24 (0.08)	-0.17 (0.07)
Runny Nose	-0.43 (0.08)	-0.47 (0.08)	-0.12 (0.08)	-0.36 (0.10)	-0.23 (0.09)
Nasal Itching	-0.38 (0.08)	-0.40 (0.07)	-0.03 (0.08)	-0.40 (0.09)	-0.14 (0.08)
Nasal Congestion	-0.41 (0.07)	-0.37 (0.07)	-0.05 (0.07)	-0.20 (0.08)	-0.06 (0.07)

35. Secondary Outcome

Title	Baseline Daily Subject-reported Individual PM Instantaneous NSS
Description	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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Baseline Nasal Sneezing	1.42 (0.89)	1.51 (0.86)	1.40 (0.93)	1.30 (0.85)	1.47 (0.92)
Baseline Runny Nose	1.80 (0.85)	2.03 (0.73)	1.98 (0.72)	2.13 (0.75)	2.01 (0.76)
Baseline Nasal Itching	1.60 (0.90)	1.88 (0.78)	1.64 (0.84)	1.79 (0.87)	1.84 (0.91)
Baseline Nasal Congestion	2.02 (0.82)	2.19 (0.59)	2.11 (0.68)	2.16 (0.76)	2.12 (0.65)

36. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported Individual PM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	50	59	57	48	58
Nasal Sneezing	-0.33 (0.08)	-0.37 (0.08)	-0.07 (0.08)	-0.24 (0.08)	-0.22 (0.08)
Runny Nose	-0.41 (0.08)	-0.45 (0.07)	-0.08 (0.08)	-0.33 (0.10)	-0.30 (0.09)
Nasal Itching	-0.32 (0.08)	-0.44 (0.07)	0.02 (0.07)	-0.35 (0.09)	-0.25 (0.08)
Nasal Congestion	-0.34 (0.07)	-0.39 (0.07)	0.02 (0.07)	-0.15 (0.09)	-0.12 (0.08)

37. Secondary Outcome

Title	Baseline Daily Subject-reported Individual AM and PM Instantaneous NSS
Description	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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Baseline Nasal Sneezing	1.33 (0.83)	1.47 (0.89)	1.37 (0.91)	1.22 (0.83)	1.38 (0.95)
Baseline Runny Nose	1.81 (0.83)	2.05 (0.67)	2.00 (0.72)	2.10 (0.69)	1.98 (0.80)
Baseline Nasal Itching	1.61 (0.86)	1.87 (0.75)	1.70 (0.84)	1.78 (0.87)	1.80 (0.89)
Baseline Nasal Congestion	2.13 (0.72)	2.23 (0.55)	2.19 (0.62)	2.20 (0.68)	2.16 (0.63)

38. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported Individual AM and PM Instantaneous NSS Averaged Over the 6 Weeks of Double-blind Treatment
Description	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 (no sign/symptom evident); = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated by subtracting baseline value from the 6-week DB average. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo	Ciclesonide Aqueous Nasal Spray 200 Mcg	AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily	AQ Nasal Spray Placebo once daily
Measure Participants	51	60	57	48	58
Nasal Sneezing	-0.32 (0.08)	-0.37 (0.07)	-0.06 (0.07)	-0.23 (0.08)	-0.20 (0.07)
Runny Nose	-0.42 (0.08)	-0.47 (0.07)	-0.10 (0.07)	-0.35 (0.09)	-0.27 (0.09)
Nasal Itching	-0.35 (0.08)	-0.42 (0.07)	-0.01 (0.07)	-0.37 (0.09)	-0.20 (0.08)
Nasal Congestion	-0.37 (0.07)	-0.39 (0.06)	-0.01 (0.06)	-0.17 (0.08)	-0.09 (0.08)

39. Secondary Outcome

Title	Time to Maximal Effect Over 6 Weeks of Double-blind Treatment.
Description	The time to maximal effect is defined as the number of days until the first treatment day on which the estimated difference between each active treatment group and corresponding 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 evaluation is made separately for each dose level of Ciclesonide HFA compared to placebo. Difference is calculated as placebo - ciclesonide. Analysis of HFA data and AQ data were conducted separately.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Analysis does not include the subjects that received Dexamethasone during the active control period.

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	Ciclesonide Aqueous Nasal Spray 200 Mcg
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily
Measure Participants	51	60	48
Number [Number of days]	15	29	7

40. Secondary Outcome

Title	Ratio (Percentage) of Correct Advances of the Dose Indicator Out of Expected Advances.
Description	Ratio of correct advance is defined as the (number of doses actuated/number of dose reported).
Time Frame	Weeks 1-2, 2-4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily
Measure Participants	51	60	75
Weeks 1-2 (n=49,58,75)	106.3 (10.8)	106.2 (12.1)	105.3 (15.8)
Weeks 2-4 (n=46,52,71)	105.6 (11.8)	105.9 (10.5)	105.8 (11.7)

41. Secondary Outcome

Title	Number of Devices With Actuation Consistency
Description	Actuation consistency is defined as a dose indicator count within ±20% of the subject self report of study medication administration.
Time Frame	Weeks 1-4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	Ciclesonide Aqueous Nasal Spray 200 Mcg
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily
Measure Participants	46	52	71
Number [Devices]	42	48	68

42. Secondary Outcome

Title	Percentage of Devices With Actuation Consistency
Description	Actuation consistency is defined as a dose indicator count within ±20% of the subject self report of study medication administration.
Time Frame	Weeks 1-4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily
Measure Participants	46	52	71
Number [percentage of devices]	91.3	92.3	95.8

43. Secondary Outcome

Title	Number of Devices With Major Discrepancies
Description	A major discrepancy is defined as a discrepancy of >20 actuations between the dose indicator and subject self report of study medication administration.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	Ciclesonide Aqueous Nasal Spray 200 Mcg
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	Ciclesonide Aqueous Nasal Spray 200 mcg once daily
Measure Participants	46	52	71
Number [Devices]	0	2	1

44. Secondary Outcome

Title	Percentage of Devices With Major Discrepancies
Description	A major discrepancy is defined as a discrepancy of >20 actuations between the dose indicator and subject self report of study medication administration.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg	Ciclesonide HFA Nasal Aerosol 160 Mcg	HFA Nasal Aerosol Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily	Ciclesonide HFA Nasal Aerosol 160 mcg once daily	HFA Nasal Aerosol Placebo once daily
Measure Participants	46	52	71
Number [percentage of devices]	0	3.8	1.4

Adverse Events

Adverse Event Reporting Description	Adverse events were NOT assessed for active control (Placebo plus Dexamethasone) groups.
Arm/Group Title	Ciclesonide HFA Nasal Aerosol 320 Mcg		Ciclesonide HFA Nasal Aerosol 160 Mcg		HFA Nasal Aerosol Placebo		Ciclesonide Aqueous Nasal Spray 200 Mcg		AQ Nasal Spray Placebo
Arm/Group Description	Ciclesonide HFA Nasal Aerosol 320 mcg once daily		Ciclesonide HFA Nasal Aerosol 160 mcg once daily		HFA Nasal Aerosol Placebo once daily		Ciclesonide Aqueous Nasal Spray 200 mcg once daily		AQ Nasal Spray Placebo once daily
All Cause Mortality
	Ciclesonide HFA Nasal Aerosol 320 Mcg		Ciclesonide HFA Nasal Aerosol 160 Mcg		HFA Nasal Aerosol Placebo		Ciclesonide Aqueous Nasal Spray 200 Mcg		AQ Nasal Spray Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ciclesonide HFA Nasal Aerosol 320 Mcg		Ciclesonide HFA Nasal Aerosol 160 Mcg		HFA Nasal Aerosol Placebo		Ciclesonide Aqueous Nasal Spray 200 Mcg		AQ Nasal Spray Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/57 (0%)		0/18 (0%)		0/47 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Ciclesonide HFA Nasal Aerosol 320 Mcg		Ciclesonide HFA Nasal Aerosol 160 Mcg		HFA Nasal Aerosol Placebo		Ciclesonide Aqueous Nasal Spray 200 Mcg		AQ Nasal Spray Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/51 (47.1%)		22/60 (36.7%)		16/57 (28.1%)		25/48 (52.1%)		22/58 (37.9%)
Ear and labyrinth disorders
Vertigo	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Endocrine disorders
Hyphthyroidism	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Eye disorders
Conjunctivitis	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	0/51 (0%)	0	0/60 (0%)	0	1/57 (1.8%)	1	1/48 (2.1%)	2	0/58 (0%)	0
Constipation	0/51 (0%)	0	0/60 (0%)	0	1/57 (1.8%)	1	1/48 (2.1%)	1	0/58 (0%)	0
Dental caries	0/51 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Diarrhoea	1/51 (2%)	1	1/60 (1.7%)	1	0/57 (0%)	0	1/48 (2.1%)	1	1/58 (1.7%)	1
Dyspepsia	1/51 (2%)	1	1/60 (1.7%)	1	0/57 (0%)	0	0/48 (0%)	0	0/58 (0%)	0
Nausea	1/51 (2%)	1	2/60 (3.3%)	2	2/57 (3.5%)	2	2/48 (4.2%)	2	2/58 (3.4%)	2
Tooth impacted	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Vomiting	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	3/48 (6.3%)	3	0/58 (0%)	0
General disorders
Asthenia	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Influenza like illness	0/51 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	0/48 (0%)	0	0/58 (0%)	0
Instillation site discomfort	2/51 (3.9%)	2	2/60 (3.3%)	2	1/57 (1.8%)	1	0/48 (0%)	0	0/58 (0%)	0
Pyrexia	1/51 (2%)	1	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Infections and infestations
Eye infection	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Gastroenteritis	0/51 (0%)	0	2/60 (3.3%)	2	0/57 (0%)	0	0/48 (0%)	0	0/58 (0%)	0
Nasopharyngitis	4/51 (7.8%)	4	2/60 (3.3%)	2	2/57 (3.5%)	2	1/48 (2.1%)	1	3/58 (5.2%)	3
Otitis Media	0/51 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	2/48 (4.2%)	2	0/58 (0%)	0
Sinusitis	0/51 (0%)	0	1/60 (1.7%)	1	1/57 (1.8%)	1	1/48 (2.1%)	1	0/58 (0%)	0
Tooth infection	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Upper respiratory tract infection	1/51 (2%)	1	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	1/58 (1.7%)	1
Urinary Tract Infection	0/51 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	0/48 (0%)	0	1/58 (1.7%)	1
Injury, poisoning and procedural complications
Arthropod bite	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Procedural Pain	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Fluid retention	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/51 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	2/48 (4.2%)	2	2/58 (3.4%)	2
Joint Swelling	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Myaglia	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	1/58 (1.7%)	1
Pain in extremity	1/51 (2%)	1	0/60 (0%)	0	0/57 (0%)	0	0/48 (0%)	0	0/58 (0%)	0
Nervous system disorders
Dizziness	0/51 (0%)	0	1/60 (1.7%)	1	1/57 (1.8%)	1	1/48 (2.1%)	1	1/58 (1.7%)	1
Drug withdrawal headache	1/51 (2%)	1	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	1/58 (1.7%)	1
Headache	2/51 (3.9%)	2	2/60 (3.3%)	2	3/57 (5.3%)	3	4/48 (8.3%)	4	7/58 (12.1%)	11
Sinus Headache	1/51 (2%)	2	0/60 (0%)	0	0/57 (0%)	0	0/48 (0%)	0	0/58 (0%)	0
Somnolence	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/48 (0%)	0	1/58 (1.7%)	1
Psychiatric disorders
Depression	0/51 (0%)	0	2/60 (3.3%)	3	0/57 (0%)	0	0/48 (0%)	0	0/58 (0%)	0
Insomnia	0/51 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	1/48 (2.1%)	1	1/58 (1.7%)	1
Panic Attack	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	2/48 (4.2%)	2	0/58 (0%)	0
Epistaxis	12/51 (23.5%)	17	4/60 (6.7%)	7	3/57 (5.3%)	3	9/48 (18.8%)	16	3/58 (5.2%)	7
Nasal mucosal disorder	1/51 (2%)	1	0/60 (0%)	0	0/57 (0%)	0	0/48 (0%)	0	2/58 (3.4%)	2
Nasal septum disorder	2/51 (3.9%)	2	0/60 (0%)	0	1/57 (1.8%)	1	1/48 (2.1%)	1	2/58 (3.4%)	2
Oropharyngeal discomfort	0/51 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/48 (2.1%)	1	0/58 (0%)	0
Oropharyngeal pain	2/51 (3.9%)	2	1/60 (1.7%)	1	0/57 (0%)	0	1/48 (2.1%)	1	1/58 (1.7%)	1
Skin and subcutaneous tissue disorders
Rash	0/51 (0%)	0	0/60 (0%)	0	1/57 (1.8%)	1	1/48 (2.1%)	1	0/58 (0%)	0

Limitations/Caveats

Dose levels investigated were higher than the US FDA approved dose (74 mcg once daily) for allergic rhinitis subjects. Publication references to 148 and 282mcg are equivalent to 160 and 320mcg.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.