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

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00953147
• Collaborator: (none)
• Enrollment: 1,110
• Locations: 45
• Arms: 3
• Duration (Months): 9
• Patients Per Site: 24.7
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Allergic Rhinitis; Perennial Allergic Rhinitis	Drug: Ciclesonide HFA 80 mcg; Drug: Ciclesonide HFA 160 mcg; Drug: Placebo	Phase 3

Detailed Description

This study will investigate the efficacy and safety of once daily ciclesonide HFA Nasal Aerosol for 26 weeks. The primary objective is to evaluate the efficacy of ciclesonide HFA (80 mcg and 160 mcg) over 6 weeks, compared to placebo in subjects with PAR. Secondary objectives are to evaluate safety and tolerability and quality of life after treatment with ciclesonide HFA (80 mcg and 160 mcg), over 6 weeks and over 6 months.

The study will consist of a Screening period (7 to 21 (±3) days) from Visit 1 to Visit 2, followed by a Single-blind Placebo Run-in period (7 to 10 days) from Visit 2 to Visit 3, followed by a 6-month (26 weeks) double-blind treatment period (Visit 3 through Visit 11). Subjects who complete this study will be allowed to participate in a 6-month open-label extension study (Study 060-635).

This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 6-Month Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of Once Daily Ciclesonide HFA Nasal Aerosol (80 and 160 μg) in The Treatment of Perennial Allergic Rhinitis (PAR) in Subjects 12 Years and Older
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ciclesonide HFA 80 mcg once daily Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Drug: Ciclesonide HFA 80 mcg; Ciclesonide HFA Nasal Aerosol 80 mcg once daily for 6 months in the treatment of Perennial Allergic Rhinitis (PAR) in subjects 12 years and older.
Experimental: Ciclesonide HFA 160 mcg once daily Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	Drug: Ciclesonide HFA 160 mcg; Ciclesonide HFA Nasal Aerosol 160 mcg once daily for 6 months in the treatment of Perennial Allergic Rhinitis (PAR) in subjects 12 years and older.
Placebo Comparator: Placebo once daily The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.	Drug: Placebo; Placebo HFA Nasal Aerosol once daily for 6 months in the treatment of Perennial Allergic Rhinitis (PAR) in subjects 12 years and older.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Daily Subject-reported AM and PM Reflective TNSS (rTNSS) Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

Secondary Outcome Measures

1. Change From Baseline in Daily Subject-reported AM and PM Instantaneous TNSS (iTNSS) Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

2. Change From Baseline in Daily Subject-reported AM rTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

3. Change From Baseline in Daily Subject-reported PM rTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

4. Change From Baseline in Daily Subject-reported AM iTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

5. Change From Baseline in Daily Subject-reported PM iTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

6. Change From Baseline in Daily Subject-reported AM rNSS Averaged Over the First 6 Weeks of the 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 = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

7. Change From Baseline in Daily Subject-reported PM rNSS Averaged Over the First 6 Weeks of the 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 = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

8. Change From Baseline in Daily Subject-reported AM & PM rNSS Averaged Over the First 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 = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

9. Change From Baseline in Daily Subject-reported AM iNSS Averaged the First 6 Weeks of the 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 = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

10. Change From Baseline in Daily Subject-reported PM iNSS Averaged the First 6 Weeks of the 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 = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

11. Change From Baseline in Daily Subject-reported AM and PM iNSS Averaged Over the First 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 = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

12. Change From Baseline to Week 6 in Rhinoconjunctivitis Quality of Life Questionnaire With Standardized [RQLQ(S)] Overall Score in Impaired Patients With Baseline RQLQ(S) Score ≥3.0 [Baseline and Week 6]

    RQLQ(S) scores in subjects with baseline RQLQ[S] score ≥3.0. RQLQ(S) consists of 28 questions, each question measured on a scale of 0-6 where a higher score indicates poor quality of life. Domains: Activities (questions 1-3), Sleep (questions 4-6), Non-Nose/Eye Symptoms (questions 7-13), Practical Problems (questions 14-16), Nasal Symptoms (questions 17-20), Eye Symptoms (questions 21-24), and Emotional (questions 25-28). The overall RQLQ(S) score was calculated as the average of the mean domain scores.

13. Change From Baseline to Month 6 (Week 26) in RQLQ(S) Overall Score in Impaired Patients With Baseline RQLQ(S) Score ≥3.0. [Baseline and Week 26]

    RQLQ(S) scores in impaired subjects with baseline RQLQ[S] score ≥3.0. RQLQ(S)consists of 28 questions, each question measured on a scale of 0-6 where a higher score indicates poor quality of life. Domains: Activities (questions 1-3), Sleep (questions 4-6), Non-Nose/Eye Symptoms (questions 7-13), Practical Problems (questions 14-16), Nasal Symptoms (questions 17-20), Eye Symptoms (questions 21-24), and Emotional (questions 25-28). The overall RQLQ(S) score was calculated as the average of the mean domain scores.

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 based on screening physical examination, medical history, and clinical laboratory values.

• If any of the Screening visit Hematology, Chemistries, or Urinalysis are not within the clinical laboratory's reference range, then the subject can be included only if the Investigator judges the deviations to be not clinically significant.

• A history of PAR to a relevant perennial allergen (house dust mites, cockroach, molds, animal dander) for a minimum of two years immediately preceding the study Screening visit. The PAR must have been of sufficient severity to have required treatment (either continuous or intermittent) in the past and require treatment throughout the entire study period.

• A demonstrated sensitivity at the Screening visit to at least one allergen known to induce PAR (house dust mite, animal dander, cockroach, and molds) using a standard skin-prick test. The subject's positive allergen test must be consistent with the medical history of PAR and must be present in the subject's environment throughout the study.

• Based upon subject's medical history, in the Investigator's judgment, the subject is unlikely to have a seasonal exacerbation during the first 6 weeks of double-blind treatment.

• Subject, if female ≤65 years of age, must have a negative serum pregnancy test at screening. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control.

Exclusion Criteria:

• Female subject who is pregnant or lactating.

• History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations; recent nasal biopsy; nasal trauma; or nasal ulcers or perforations. Surgery and atrophic rhinitis or rhinitis medicamentosa are not permitted within the last 60 days prior to the Screening visit.

• Subject is, in the investigator's judgement, having a seasonal exacerbation at the time of screening.

• Participation in any investigational drug trial within the 30 days preceding the Screening visit or planned participation in another investigational drug trial at any time during this trial.

• A known hypersensitivity to any corticosteroid or any of the excipients in the formulation of ciclesonide.

• History of a respiratory infection or disorder [including, but not limited to bronchitis, pneumonia, influenza, severe acute respiratory syndrome (SARS)] within the 14 days preceding the Screening visit.

• History of alcohol or drug abuse within 2 years preceding the Screening visit .

• History of a positive test for HIV, hepatitis B or hepatitis C.

• Active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta agonists and any controller drugs (eg, theophylline, leukotriene antagonists, etc.); intermittent use (less than or equal to 3 uses per week) of inhaled short acting beta-agonists is acceptable. Use of short acting beta-agonists for exercise-induced bronchospasm will be allowed.

• Expected use of any disallowed concomitant medications during the treatment period.

• Initiation of immunotherapy during the study period or dose escalation during the study period. However, initiation of immunotherapy 90 days or more prior to the Screening Visit and use of a stable (maintenance) dose (30 days or more) may be considered for inclusion.

• Previous participation in an intranasal ciclesonide HFA nasal aerosol study.

• Non-vaccinated exposure to or active infection with, chickenpox or measles within the 21 days preceding the Screening Visit.

• Initiation of pimecrolimus cream 1% or greater or tacrolimus ointment 0.03% or greater during the study period or planned dose escalation during the study period.

• Study participation by clinical investigator site employees and/or their immediate relatives who reside in the same household.

• Study participation by more than one subject from the same household.

• Have any of the following conditions that are judged by the investigator to be clinically significant and/or affect the subject's ability to participate in the clinical trial:

• impaired hepatic function including alcohol related liver disease or cirrhosis

• history of ocular disturbances, eg, glaucoma or posterior subcapsular cataracts

• any systemic infection

• hematological, hepatic, renal, endocrine (except for controlled diabetes mellitus or postmenopausal symptoms or hypothyroidism)

• gastrointestinal disease

• malignancy (excluding basal cell carcinoma)

• current neuropsychological condition with or without drug therapy • Any condition that, in the judgment of the investigator, would preclude the subject from completing the protocol with capture of the assessments as written.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asthma and Allergy Specialists Medical Group	Huntington Beach	California	United States	92647
2	California Allergy and Asthma Medical Group	Los Angeles	California	United States	90025
3	Southern California Research	Mission Viejo	California	United States	92691
4	CHOC PSF, AMC, Division of Allergy Asthma & Immunology	Orange	California	United States	92868
5	California Allerga and Asthma Medical Group	Palmdale	California	United States	93551
6	Allergy Associates Medical Group	San Diego	California	United States	92120
7	Allergy and Asthma Medical Group and Research Center	San Diego	California	United States	92123
8	Bensch Research Associates	Stockton	California	United States	95207
9	Asthma and Allergy Associates, P.C.	Colorado Springs	Colorado	United States	80907
10	Storms Clinical Research Institute	Colorado Springs	Colorado	United States	80907
11	Colorado Allergy and Asthma Centers	Denver	Colorado	United States	80230
12	Clinical Research Atlanta	Atlanta	Georgia	United States	30342
13	DataQuest Medical Research, LLC	Lawrenceville	Georgia	United States	30046
14	Allergy and Asthma Consultants, PC	Lilburn	Georgia	United States	30047
15	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
16	Clinical Research Center of Indiana	Indianapolis	Indiana	United States	46208
17	Gordon D. Raphael, MD	Bethesda	Maryland	United States	20814
18	Northeast Medical Research Associates, Inc.	North Dartmouth	Massachusetts	United States	02747
19	The Clinical Research Center, LLC	St. Louis	Missouri	United States	63141
20	Clinical Research Group of Montana	Bozeman	Montana	United States	59718
21	Princeton Center for Clinical Research	Skillman	New Jersey	United States	08558
22	Allergy and Asthma Center of NC	High Point	North Carolina	United States	27262
23	North Carolina Clinical Research	Raleigh	North Carolina	United States	26707
24	Toledo Center for Clinical Research	Sylvania	Ohio	United States	43560
25	Allergy and Asthma Research Group	Eugene	Oregon	United States	97401
26	Baker Allergy, Asthma and Dermatology Research Center, LLC	Lake Oswego	Oregon	United States	97035
27	Allergy Associates Research Center	Portland	Oregon	United States	97213
28	Valley Clinical Research Center	Bethlehem	Pennsylvania	United States	18020
29	Asthma and Allergy Research Associates	Upland	Pennsylvania	United States	19013
30	Asthma, Nasal Disease and Allergy Research Center of New England	Providence	Rhode Island	United States	02906
31	National Allergy, Asthma, and Urticaria	Charleston	South Carolina	United States	29406
32	Allergy and Asthma Associates	Austin	Texas	United States	78731
33	Sirius Clinical Research	Austin	Texas	United States	78759
34	Hill Country Family Medical Center	Boerne	Texas	United States	78006
35	Pharmaceutical Research and Consulting	Dallas	Texas	United States	75231
36	Western Sky Medical Research	El Paso	Texas	United States	79903
37	North Texas Institute for Clinical Trials	Fort Worth	Texas	United States	76132
38	Allergy and Asthma Associates	Houston	Texas	United States	77054
39	Kerrville Research Associates, PA	Kerrville	Texas	United States	78028
40	Kerrville Research Associates	Kerrville	Texas	United States	78028
41	Central Texas Health Research	New Braunfels	Texas	United States	78130
42	Biogenics Research Institute	San Antonio	Texas	United States	78229
43	Southwest Allergy and Asthma Center	San Antonio	Texas	United States	78229
44	Sylvana Research Associates	San Antonio	Texas	United States	78229
45	ASTHMA, Inc.	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Sunovion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT00953147
• Other Study ID Numbers: 060-633
• First Posted: Aug 6, 2009
• Last Update Posted: Jun 13, 2012
• Last Verified: Jun 1, 2012

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Ciclesonide

Study Results

Participant Flow

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Period Title: Overall Study
STARTED	298	505	307
COMPLETED	261	439	265
NOT COMPLETED	37	66	42

Baseline Characteristics

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily	Total
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.	Total of all reporting groups
Overall Participants	298	505	307	1110
Age (Count of Participants)
<=18 years	27 9.1%	44 8.7%	17 5.5%	88 7.9%
Between 18 and 65 years	264 88.6%	455 90.1%	282 91.9%	1001 90.2%
>=65 years	7 2.3%	6 1.2%	8 2.6%	21 1.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.5 (14.3)	36.5 (13.2)	38.0 (13.1)	37.2 (13.5)
Sex: Female, Male (Count of Participants)
Female	196 65.8%	310 61.4%	210 68.4%	716 64.5%
Male	102 34.2%	195 38.6%	97 31.6%	394 35.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	62 20.8%	94 18.6%	60 19.5%	216 19.5%
Not Hispanic or Latino	236 79.2%	411 81.4%	247 80.5%	894 80.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity (participants) [Number]
White/Caucasian	249 83.6%	420 83.2%	253 82.4%	922 83.1%
Black or African American	40 13.4%	65 12.9%	41 13.4%	146 13.2%
Asian	3 1%	5 1%	10 3.3%	18 1.6%
American Indian or Alaska Native	2 0.7%	0 0%	0 0%	2 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	4 0.8%	0 0%	4 0.4%
Other	3 1%	6 1.2%	3 1%	12 1.1%
Multiple	1 0.3%	5 1%	0 0%	6 0.5%
Baseline Reflective Total Nasal Symptom Score (rTNSS) (units on a scale) [Mean (Standard Deviation) ]
AM	8.51 (1.89)	8.48 (1.88)	8.60 (1.96)	8.52 (1.90)
PM	8.53 (1.91)	8.54 (1.84)	8.64 (1.92)	8.57 (1.88)
AM and PM	8.53 (1.82)	8.50 (1.81)	8.62 (1.88)	8.54 (1.83)
Baseline Instanteous Total Nasal Symptom Score (iTNSS) (units on a scale) [Mean (Standard Deviation) ]
AM	7.93 (2.27)	7.89 (2.24)	8.01 (2.37)	7.93 (2.29)
PM	7.38 (2.43)	7.38 (2.41)	7.39 (2.55)	7.38 (2.46)
AM and PM	7.66 (2.28)	7.64 (2.27)	7.70 (2.38)	7.66 (2.30)
Baseline Reflective Nasal Symptom Score (rNSS) (units on a scale) [Mean (Standard Deviation) ]
AM Sneezing	1.73 (0.73)	1.71 (0.72)	1.75 (0.74)	1.73 (0.73)
AM Runny Nose	2.24 (0.59)	2.22 (0.59)	2.28 (0.60)	2.24 (0.59)
AM Nasal Itching	2.06 (0.64)	2.08 (0.62)	2.09 (0.69)	2.08 (0.64)
AM Nasal Congestion	2.48 (0.49)	2.46 (0.49)	2.47 (0.53)	2.47 (0.50)
PM Sneezing	1.81 (0.68)	1.81 (0.70)	1.88 (0.69)	1.83 (0.69)
PM Runny Nose	2.23 (0.59)	2.23 (0.60)	2.27 (0.60)	2.24 (0.60)
PM Nasal Itching	2.08 (0.64)	2.12 (0.60)	2.12 (0.69)	2.11 (0.64)
PM Nasal Congestion	2.42 (0.53)	2.38 (0.52)	2.38 (0.54)	2.39 (0.53)
AM and PM Sneezing	1.77 (0.68)	1.76 (0.69)	1.81 (0.69)	1.78 (0.69)
AM and PM Runny Nose	2.24 (0.56)	2.22 (0.58)	2.27 (0.58)	2.24 (0.57)
AM and PM Nasal Itching	2.07 (0.62)	2.10 (0.60)	2.11 (0.67)	2.09 (0.62)
AM and PM Nasal Congestion	2.45 (0.48)	2.42 (0.48)	2.42 (0.51)	2.43 (0.49)
Baseline Instantaneous Nasal Symptom Score (iNSS) (units on a scale) [Mean (Standard Deviation) ]
AM Sneezing	1.38 (0.91)	1.40 (0.88)	1.43 (0.93)	1.40 (0.91)
AM Runny Nose	2.14 (0.68)	2.13 (0.68)	2.20 (0.67)	2.15 (0.68)
AM Nasal Itching	2.00 (0.72)	1.99 (0.69)	2.00 (0.76)	2.00 (0.72)
AM Nasal Congestion	2.41 (0.53)	2.38 (0.56)	2.38 (0.60)	2.39 (0.57)
PM Sneezing	1.30 (0.90)	1.32 (0.89)	1.36 (0.90)	1.32 (0.90)
PM Runny Nose	1.98 (0.73)	1.98 (0.74)	2.02 (0.72)	1.99 (0.73)
PM Nasal Itching	1.87 (0.73)	1.90 (0.71)	1.83 (0.80)	1.87 (0.74)
PM Nasal Congestion	2.22 (0.61)	2.19 (0.63)	2.17 (0.66)	2.19 (0.63)
AM and PM Sneezing	1.35 (0.89)	1.36 (0.86)	1.39 (0.89)	1.36 (0.88)
AM and PM Runny Nose	2.06 (0.67)	2.05 (0.68)	2.11 (0.65)	2.07 (0.67)
AM and PM Nasal Itching	1.94 (0.70)	1.95 (0.68)	1.91 (0.75)	1.93 (0.70)
AM and PM Nasal Congestion	2.32 (0.54)	2.28 (0.57)	2.28 (0.60)	2.29 (0.57)
Baseline Rhinoconjunctivitis Quality of Life Questionnaire score [RQLQ (S)] )≥3.0 (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.16 (0.77)	4.05 (0.76)	4.12 (0.78)	4.10 (0.77)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Daily Subject-reported AM and PM Reflective TNSS (rTNSS) Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Least Squares Mean (Standard Error) [units on a scale]	-1.97 (0.13)	-1.82 (0.10)	-1.28 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide HFA 80 Mcg Once Daily, Placebo Once Daily
	Comments	The null hypothesis is that there is no difference in primary outcome when compare active to placebo group. The alternative hypothesis is that there is a difference in primary outcome when compare active to placebo group. It was estimated that 200 subjects per group will provide at least 85% power to detect a difference between treatment groups of 0.7 in the change from baseline in iTNSS with a two-sided alpha level of 0.025.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value from primary outcome was adjusted at alpha=0.025.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.35 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide HFA 160 Mcg Once Daily, Placebo Once Daily
	Comments	The null hypothesis is that there is no difference in primary outcome when compare active to placebo group. The alternative hypothesis is that there is a difference in primary outcome when compare active to placebo group. It was estimated that 200 subjects per group will provide at least 85% power to detect a difference between treatment groups of 0.7 in the change from baseline in iTNSS with a two-sided alpha level of 0.025.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	The p-value from primary outcome was adjusted at alpha=0.025.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM and PM Instantaneous TNSS (iTNSS) Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Least Squares Mean (Standard Error) [units on a scale]	-1.77 (0.12)	-1.60 (0.10)	-1.18 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide HFA 80 Mcg Once Daily, Placebo Once Daily
	Comments	Dmitrienko's tree-structured gatekeeping method was used for multiple comparisons
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ciclesonide HFA 160 Mcg Once Daily, Placebo Once Daily
	Comments	Dmitrienko's tree-structured gatekeeping method was used for multiple comparisons
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0122
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM rTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	297	503	304
Least Squares Mean (Standard Error) [units on a scale]	-1.94 (0.13)	-1.78 (0.10)	-1.25 (0.13)

4. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported PM rTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Least Squares Mean (Standard Error) [units on a scale]	-2.01 (0.13)	-1.88 (0.10)	-1.32 (0.13)

5. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM iTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all participants analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	297	503	304
Least Squares Mean (Standard Error) [units on a scale]	-1.78 (0.12)	-1.67 (0.10)	-1.23 (0.12)

6. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported PM iTNSS Averaged Over the First 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 symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Least Squares Mean (Standard Error) [units on a scale]	-1.76 (0.13)	-1.55 (0.10)	-1.15 (0.13)

7. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM rNSS Averaged Over the First 6 Weeks of the 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 = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0 - 6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	297	503	304
Sneezing	-0.51 (0.04)	-0.47 (0.03)	-0.31 (0.04)
Runny Nose	-0.49 (0.04)	-0.44 (0.03)	-0.31 (0.04)
Nasal Itching	-0.52 (0.04)	-0.48 (0.03)	-0.38 (0.04)
Nasal Congestion	-0.42 (0.03)	-0.38 (0.03)	-0.25 (0.03)

8. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported PM rNSS Averaged Over the First 6 Weeks of the 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 = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Sneezing	-0.53 (0.04)	-0.52 (0.03)	-0.35 (0.04)
Runny Nose	-0.51 (0.04)	-0.47 (0.03)	-0.31 (0.04)
Nasal Itching	-0.54 (0.04)	-0.51 (0.03)	-0.39 (0.04)
Nasal Congestion	-0.43 (0.03)	-0.39 (0.03)	-0.26 (0.03)

9. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM & PM rNSS Averaged Over the First 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 = mild = moderate = severe Reflective NSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Sneezing	-0.52 (0.04)	-0.49 (0.03)	-0.33 (0.04)
Runny Nose	-0.50 (0.04)	-0.45 (0.03)	-0.31 (0.04)
Nasal Itching	-0.53 (0.04)	-0.49 (0.03)	-0.39 (0.04)
Nasal Congestion	-0.42 (0.03)	-0.39 (0.03)	-0.26 (0.03)

10. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM iNSS Averaged the First 6 Weeks of the 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 = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	297	503	304
Sneezing	-0.45 (0.04)	-0.44 (0.03)	-0.34 (0.04)
Runny Nose	-0.47 (0.04)	-0.43 (0.03)	-0.30 (0.04)
Nasal Itching	-0.51 (0.04)	-0.47 (0.03)	-0.37 (0.04)
Nasal Congestion	-0.36 (0.03)	-0.33 (0.02)	-0.22 (0.03)

11. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported PM iNSS Averaged the First 6 Weeks of the 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 = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	505	307
Sneezing	-0.44 (0.04)	-0.39 (0.03)	-0.31 (0.04)
Runny Nose	-0.47 (0.04)	-0.40 (0.03)	-0.29 (0.04)
Nasal Itching	-0.49 (0.04)	-0.45 (0.03)	-0.33 (0.04)
Nasal Congestion	-0.37 (0.03)	-0.31 (0.03)	-0.22 (0.03)

12. Secondary Outcome

Title	Change From Baseline in Daily Subject-reported AM and PM iNSS Averaged Over the First 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 = mild = moderate = severe Instantaneous NSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the six week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Time Frame	Weeks 0-6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	298	504	305
Sneezing	-0.44 (0.04)	-0.41 (0.03)	-0.32 (0.04)
Runny Nose	-0.47 (0.04)	-0.41 (0.03)	-0.30 (0.04)
Nasal Itching	-0.50 (0.04)	-0.46 (0.03)	-0.35 (0.04)
Nasal Congestion	-0.36 (0.03)	-0.32 (0.02)	-0.22 (0.03)

13. Secondary Outcome

Title	Change From Baseline to Week 6 in Rhinoconjunctivitis Quality of Life Questionnaire With Standardized [RQLQ(S)] Overall Score in Impaired Patients With Baseline RQLQ(S) Score ≥3.0
Description	RQLQ(S) scores in subjects with baseline RQLQ[S] score ≥3.0. RQLQ(S) consists of 28 questions, each question measured on a scale of 0-6 where a higher score indicates poor quality of life. Domains: Activities (questions 1-3), Sleep (questions 4-6), Non-Nose/Eye Symptoms (questions 7-13), Practical Problems (questions 14-16), Nasal Symptoms (questions 17-20), Eye Symptoms (questions 21-24), and Emotional (questions 25-28). The overall RQLQ(S) score was calculated as the average of the mean domain scores.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	109	191	101
Least Squares Mean (Standard Error) [units on a scale]	-1.55 (0.13)	-1.27 (0.11)	-0.96 (0.14)

14. Secondary Outcome

Title	Change From Baseline to Month 6 (Week 26) in RQLQ(S) Overall Score in Impaired Patients With Baseline RQLQ(S) Score ≥3.0.
Description	RQLQ(S) scores in impaired subjects with baseline RQLQ[S] score ≥3.0. RQLQ(S)consists of 28 questions, each question measured on a scale of 0-6 where a higher score indicates poor quality of life. Domains: Activities (questions 1-3), Sleep (questions 4-6), Non-Nose/Eye Symptoms (questions 7-13), Practical Problems (questions 14-16), Nasal Symptoms (questions 17-20), Eye Symptoms (questions 21-24), and Emotional (questions 25-28). The overall RQLQ(S) score was calculated as the average of the mean domain scores.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Not all subjects analyzed due to missing data.

Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily	Ciclesonide HFA 160 Mcg Once Daily	Placebo Once Daily
Arm/Group Description	Ciclesonide HFA nasal aerosol will be supplied in a 40 mcg canister, to be administered as 1 puff in each nostril (80 mcg per day).	Ciclesonide HFA nasal aerosol will be supplied in a 80 mcg canister, to be administered as 1 puff in each nostril (160 mcg per day).	The placebo HFA nasal aerosol is identical to active drug, but does not contain ciclesonide.
Measure Participants	100	160	86
Least Squares Mean (Standard Error) [units on a scale]	-1.67 (0.14)	-1.62 (0.11)	-1.40 (0.15)

Adverse Events

Time Frame	6 Months
Arm/Group Title	Ciclesonide HFA 80 Mcg Once Daily		Ciclesonide HFA 160 Mcg Once Daily		Placebo Once Daily
Arm/Group Description
All Cause Mortality
	Ciclesonide HFA 80 Mcg Once Daily		Ciclesonide HFA 160 Mcg Once Daily		Placebo Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ciclesonide HFA 80 Mcg Once Daily		Ciclesonide HFA 160 Mcg Once Daily		Placebo Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/298 (2%)		8/505 (1.6%)		6/307 (2%)
Blood and lymphatic system disorders
Thrombocytopenia	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Cardiac disorders
Artrioventricular block second degree	0/298 (0%)	0	0/505 (0%)	0	1/307 (0.3%)	1
Gastrointestinal disorders
Diverticular perforation	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Colonic atony	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Megacolon	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Pancreatitis	0/298 (0%)	0	0/505 (0%)	0	2/307 (0.7%)	2
Vomiting	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
General disorders
Hernia obstructive	0/298 (0%)	0	0/505 (0%)	0	1/307 (0.3%)	1
Infections and infestations
Appendicitis	1/298 (0.3%)	1	0/505 (0%)	0	0/307 (0%)	0
Pneumonia	1/298 (0.3%)	1	0/505 (0%)	0	0/307 (0%)	0
Musculoskeletal and connective tissue disorders
Scleroderma	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Nervous system disorders
Embolic cerebral infarction	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Mononeuropathy mulitplex	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Abortion spontaneous	1/298 (0.3%)	1	0/505 (0%)	0	1/307 (0.3%)	1
Psychiatric disorders
Suicidal ideation	1/298 (0.3%)	1	0/505 (0%)	0	0/307 (0%)	0
Reproductive system and breast disorders
Ovarian Cyst	1/298 (0.3%)	1	0/505 (0%)	0	0/307 (0%)	0
Pelvic adhesions	1/298 (0.3%)	1	0/505 (0%)	0	0/307 (0%)	0
Cystocele	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Rectocele	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/298 (0%)	0	0/505 (0%)	0	1/307 (0.3%)	1
Social circumstances
Imprisonment	0/298 (0%)	0	1/505 (0.2%)	1	0/307 (0%)	0
Vascular disorders
Hypertension	0/298 (0%)	0	0/505 (0%)	0	1/307 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Ciclesonide HFA 80 Mcg Once Daily		Ciclesonide HFA 160 Mcg Once Daily		Placebo Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	148/334 (44.3%)		234/475 (49.3%)		131/243 (53.9%)
Gastrointestinal disorders
Abdominal pain	4/334 (1.2%)	4	7/475 (1.5%)	8	7/243 (2.9%)	7
Nausea	9/334 (2.7%)	10	8/475 (1.7%)	8	2/243 (0.8%)	2
General disorders
Instillation site discomfort	10/334 (3%)	11	9/475 (1.9%)	11	0/243 (0%)	0
Infections and infestations
Bronchitis	7/334 (2.1%)	7	11/475 (2.3%)	11	6/243 (2.5%)	6
Influenza	6/334 (1.8%)	6	9/475 (1.9%)	11	3/243 (1.2%)	4
Nasopharyngitis	14/334 (4.2%)	17	30/475 (6.3%)	35	19/243 (7.8%)	26
Pharyngitis streptococcal	7/334 (2.1%)	8	5/475 (1.1%)	5	5/243 (2.1%)	6
Sinusitis	14/334 (4.2%)	16	27/475 (5.7%)	30	17/243 (7%)	18
Upper respiratory tract infection	43/334 (12.9%)	54	66/475 (13.9%)	74	29/243 (11.9%)	37
Urinary tract infection	13/334 (3.9%)	13	14/475 (2.9%)	16	9/243 (3.7%)	10
Viral upper respiratory tract infection	15/334 (4.5%)	16	13/475 (2.7%)	14	7/243 (2.9%)	9
Injury, poisoning and procedural complications
Muscle strain	6/334 (1.8%)	7	7/475 (1.5%)	9	2/243 (0.8%)	2
Musculoskeletal and connective tissue disorders
Back pain	5/334 (1.5%)	12	11/475 (2.3%)	11	10/243 (4.1%)	12
Nervous system disorders
Headache	21/334 (6.3%)	36	17/475 (3.6%)	27	14/243 (5.8%)	18
Sinus headache	6/334 (1.8%)	10	4/475 (0.8%)	7	7/243 (2.9%)	8
Respiratory, thoracic and mediastinal disorders
Cough	9/334 (2.7%)	9	19/475 (4%)	19	8/243 (3.3%)	9
Epistaxis	34/334 (10.2%)	57	57/475 (12%)	98	24/243 (9.9%)	42
Nasal discomfort	8/334 (2.4%)	9	16/475 (3.4%)	16	2/243 (0.8%)	2
Nasal mucosal disorder	7/334 (2.1%)	7	12/475 (2.5%)	14	2/243 (0.8%)	2
Nasal septum disorder	5/334 (1.5%)	6	16/475 (3.4%)	21	3/243 (1.2%)	4
Oropharyngeal pain	12/334 (3.6%)	15	20/475 (4.2%)	22	10/243 (4.1%)	11
Vascular disorders
Hypertension	4/334 (1.2%)	4	7/475 (1.5%)	8	8/243 (3.3%)	8

Limitations/Caveats

This study was not designed or powered for a comparison of the 80mcg dose with the 160mcg dose therefore no statistical comparisons were planned between the two active groups. Publication references to 74 and 148mcg are equivalent to 80 and 160mcg

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Certain Agreements

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