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

A 2-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Safety and Efficacy Study of Ciclesonide Nasal Aerosol in Subjects 6 to 11 Years With Seasonal Allergic Rhinitis

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01458275

Enrollment

847

Registered

2011-10-24

Start date

2011-11-30

Completion date

2013-03-31

Last updated

2014-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Seasonal Allergic Rhinitis

Keywords

Seasonal Allergic Rhinitis, Ciclesonide, Ciclesonide Nasal Aerosol

Brief summary

Detailed description

This is a 2-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, efficacy and safety study of ciclesonide nasal aerosol administered once daily to male and premenarchal female subjects 6 to 11 years-old diagnosed with SAR. This study will consist of the following: Screening, Single-blind Placebo Run-in period, Double-blind Treatment period (during this period, subjects will be randomized to double-blind treatment with either ciclesonide nasal aerosol 37 mcg or 74 mcg or placebo for 2 weeks of treatment) and Follow-up. The total duration of subject participation will be approximately 2 months.

Interventions

DRUGCiclesonide nasal aerosol 37 mcg

ciclesonide nasal aerosol 37mcg - the dose is administered as 1 actuation per nostril to give a total dose of 37 mcg

DRUGciclesonide nasal aerosol 74 mcg

ciclesonide nasal aerosol 74 mcg - the dose is administered as 1 actuation per nostril to give a total dose of 74 mcg

DRUGPlacebo

Placebo - one actuation per nostril

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

6 Years to 11 Years

Healthy volunteers

Inclusion criteria

* Gives written informed consent (parent/legal guardian) and assent (from the child), including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation. * Is a male or premenarchal female 6 to 11 years-old at the screening. * Is in general good health (defined as the absence of any clinically relevant abnormalities as determined by the investigator) based on screening physical examination and medical history. * Has a history of SAR to any relevant dominant seasonal allergen for a minimum of one to two years immediately preceding the study Screening Visit. The SAR must have been of sufficient severity to have required treatment (either continuous or intermittent) in the past and is expected to require treatment throughout the entire study period. * Has a demonstrated sensitivity to a relevant dominant seasonal allergen known to induce SAR based on a documented result with a standard skin prick test either within 12 months 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 control wheal (normal saline) for the skin prick test. The subject's positive allergen test must be consistent with the medical history of SAR, and the allergen must be present in the subject's environment throughout the study. * Subject or parent/guardian must possess an educational level and degree of understanding of English that enables them to communicate suitably with the Investigator and study coordinator as well as accurately complete both the Allergic Rhinitis diary and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ).

Exclusion criteria

* Has a history of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations; recent unhealed nasal biopsy; nasal trauma; or nasal ulcers or perforations. Surgery and atrophic rhinitis or rhinitis medicamentosa are not permitted within the 120 days prior to the screening visit. * Has evidence of infection, significant anatomic abnormality, ulceration of the mucosa, blood in the nose, or any other clinically relevant finding on nasal examination at the screening visit. * Has nasal jewelry * Has participated in any investigational drug trial within the 30 days preceding the screening visit or is planning participation in another investigational drug trial at any time during this trial. * Has a known hypersensitivity to any corticosteroid or any of the excipients in the formulation of ciclesonide. * Has a history of a respiratory infection or disorder, including but not limited to bronchitis, pneumonia, influenza, and severe acute respiratory syndrome (SARS), within the 14 days preceding the screening visit. * Has active asthma requiring treatment with inhaled or systemic corticosteroids and/or routine use of beta-agonists and any controller drugs (eg, theophylline, leukotriene antagonists); intermittent use (≤ 3 uses per week) of inhaled short-acting beta-agonists is acceptable. Use of short-acting beta agonists for exercise induced bronchospasm will be allowed. * Plans to travel outside the study area (the known pollen area for the investigative site) for 2 or more consecutive days between Randomization Visit and the final Treatment Visit. * Plans to leave the study area (the known pollen area for the investigative site) for longer than 24 hours during the Single-blind Placebo Run-in period. * Is expecting to use any disallowed concomitant medications during the treatment period. * Is planning initiation of immunotherapy during the study period or dose escalation during the study period. However, initiation of immunotherapy 90 days or more prior to the screening visit and use of a stable (maintenance) dose (30 days or more) may be considered for inclusion. * Has nonvaccinated exposure to or active infection with chickenpox or measles within the 21 days preceding the screening visit. * Initiates pimecrolimus cream 1% or greater or tacrolimus ointment 0.03% or greater during the study period or plans a dose escalation during the study period. However, initiation of these creams/ointments 30 days or more prior to screening and use of a stable (maintenance) dose during the study period may be considered for inclusion. * Is a child or relative of any clinical investigator or site personnel, even those who are not directly involved in this study. * Has any of the following conditions that are judged by the investigator to be clinically significant and/or to affect the subject's ability to participate in the clinical trial: impaired hepatic function; history of ocular disturbances, eg, glaucoma or posterior subcapsular cataracts or herpes simplex; any systemic infection hematological (including anemia), hepatic, renal, endocrine disease; gastrointestinal disease; malignancy (excluding basal cell carcinoma); current neuropsychological condition with or without drug therapy. Any behavioral condition that could affect subject's ability to accurately report symptoms to the caregiver such as developmental delay, attention deficit disorder, and autism. * Has any condition that, in the judgment of the investigator, would preclude the subject from completing the protocol with capture of the assessments as written. * Has received ciclesonide nasal aerosol in a previous clinical trial

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change From Baseline in Average Daily Subject-reported AM and PM Reflective Total Ocular Symptom Scores (rTOSS) Over the 2-week Double-blind Treatment Period.	Weeks 0 - 2	TOSS is the sum of individual ocular symptoms of itching, tearing, and redness. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1. = mild 2. = moderate 3. = severe Therefore, TOSS ranges from 0-9 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TOSS symptom scores assess symptoms over the previous 12-hour time interval. Difference was calculated as the two week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Change From Baseline in the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Overall Score at the End of the Double-blind Treatment Period.	Weeks 0 - 2	PRQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with rhinoconjunctivitis. The PRQLQ has 23 questions in 5 domains (nose symptoms, eye symptoms, practical problems, activity limitation, and other symptoms). Children recalled how they were during the previous week and responded to each question on a 7-point scale (0 = not bothered to 6 = extremely bothered or 0 = none of the time to 6 = all of the time) for a total possible score of 138. The overall PRQLQ score is the mean of all 23 responses and the individual domain scores are the means of the items in those domains.
Change From Baseline in Average Daily Subject Reported AM Instantaneous Total Nasal Symptom Scores (iTNSS) Over the 2-week Double-blind Treatment Period	Weeks 0 - 2	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions assessed in the AM. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe in the AM. 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 two week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Change From Baseline in Average Daily Subject-reported AM and PM Instantaneous Total Ocular Symptom Scores (iTOSS) Over the 2-week Double-blind Treatment Period.	Weeks 0 - 2	TOSS is the sum of individual ocular symptoms of itching, tearing, and redness. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1. = mild 2. = moderate 3. = severe Therefore, TOSS ranges from 0-9 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TOSS symptom scores assess symptoms over the previous 10 minute time interval. Difference was calculated as the two week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement
Time to Maximal Effect in the AM and PM Reflective Total Nasal Symptom Scores (rTNSS) Over the 2-week Double-blind Treatment Period	Weeks 0 - 2	The time to maximal effect, defined as the number of days until the first treatment day on which the estimated difference between ciclesonide nasal aerosol and placebo was at least 90% of the largest estimated difference, was based on the analyses of change from baseline in the average of AM and PM rTNSS scores for each day. The time to achieve at least 90% of these estimated differences is presented.
Change From Baseline in Average Daily Subject-reported AM and PM Instantaneous Total Nasal Symptom Scores (iTNSS) Over the 2-week Double-blind Treatment Period	Weeks 0 - 2	TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the two week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.
Percentage of Subjects Experiencing Treatment-emergent AEs	Weeks 0 - 3	Treatment-Emergent Adverse Events Occurring in ≥ 2% of Subjects in Any Treatment Group (ITT Population)
Treatment-emergent AEs Causing Study Medication Discontinuation	Weeks 0 - 3	—
Number of Subjects Experiencing Treatment-emergent Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation	Weeks 0 - 3	—
Percentage of Subjects Experiencing Treatment-emergent Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation	Weeks 0 - 3	—
Number of Subjects Experiencing Treatment-emergent AEs	Weeks 0 - 3	Treatment-Emergent Adverse Events Occurring in ≥ 2% of Subjects in Any Treatment Group (ITT Population)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Placebo Placebo: Placebo - one actuation per nostril	283
Ciclesonide Nasal Aerosol 37mcg ciclesonide nasal aerosol 37mcg - the dose is administered as 1 actuation per nostril to give a total dose of 37 mcg	282
Ciclesonide Nasal Aerosol 74 mcg ciclesonide nasal aerosol 74 mcg - the dose is administered as 1 actuation per nostril to give a total dose of 74 mcg	282
Total	847

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	3	4	1
Overall Study	Lost to Follow-up	3	2	5
Overall Study	Protocol Violation	5	5	2
Overall Study	Withdrawal by Subject	3	2	1

Baseline characteristics

Characteristic	Ciclesonide Nasal Aerosol 37mcg	Ciclesonide Nasal Aerosol 74 mcg	Placebo	Total
Age, Categorical <=18 years	282 Participants	282 Participants	283 Participants	847 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Continuous	8.5 years STANDARD_DEVIATION 1.64	8.7 years STANDARD_DEVIATION 1.65	8.6 years STANDARD_DEVIATION 1.72	8.6 years STANDARD_DEVIATION 1.65
Age, Customized 6-8 Years	123 participants	120 participants	131 participants	374 participants
Age, Customized 9-11 Years	159 participants	162 participants	152 participants	473 participants
Region of Enrollment United States	282 participants	282 participants	283 participants	847 participants
Sex: Female, Male Female	123 Participants	120 Participants	131 Participants	374 Participants
Sex: Female, Male Male	159 Participants	162 Participants	152 Participants	473 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	25 / 283	31 / 282	24 / 282
serious Total, serious adverse events	0 / 283	1 / 282	0 / 282

Outcome results

Primary

Change From Baseline in Average Daily Subject Reported AM and PM Reflective Total Nasal Symptom Scores (rTNSS) Over the 2-week Double-blind Treatment Period

TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe. Therefore, rTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Reflective TNSS measures these symptoms over the previous 12-hour time interval. Difference was calculated as the two week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

Time frame: Weeks 0 - 2

Population: n = number of ITT subjects in treatmentgroup with completed assessment

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Change From Baseline in Average Daily Subject Reported AM and PM Reflective Total Nasal Symptom Scores (rTNSS) Over the 2-week Double-blind Treatment Period	-1.63 units on a scale	Standard Error 0.133
Ciclesonide Nasal Aerosol 37mcg	Change From Baseline in Average Daily Subject Reported AM and PM Reflective Total Nasal Symptom Scores (rTNSS) Over the 2-week Double-blind Treatment Period	-1.73 units on a scale	Standard Error 0.133
Ciclesonide Nasal Aerosol 74 mcg	Change From Baseline in Average Daily Subject Reported AM and PM Reflective Total Nasal Symptom Scores (rTNSS) Over the 2-week Double-blind Treatment Period	-1.61 units on a scale	Standard Error 0.133

Secondary

Change From Baseline in Average Daily Subject-reported AM and PM Instantaneous Total Nasal Symptom Scores (iTNSS) Over the 2-week Double-blind Treatment Period

TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 1 = mild 2 = moderate 3 = severe Therefore, iTNSS values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). Instantaneous TNSS measures these symptoms over the previous 10 minute time interval. Difference was calculated as the two week treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.

Time frame: Weeks 0 - 2