Trial Outcomes & Findings for Safety Study of the Potential Inhibitory Effects of Ciclesonide Nasal Aerosol on the Hypothalamic-Pituitary-Adrenal Axis in Subjects 6-11 Years With Perennial Allergic Rhinitis (NCT NCT01378429)

NCT ID: NCT01378429

Last Updated: 2014-05-26

Results Overview

Area under the concentration-time curve from time 0 to 24 hours \[AUC(0-24h)\]. Timepoints at which data were collected: 0, 2, 4, 8, 12, 16, and 24 at week 0 and 6.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

89 participants

Primary outcome timeframe

Week 0 and 6

Results posted on

2014-05-26

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Placebo: Placebo
Ciclesonide Nasal Aerosol
ciclesonide nasal aerosol (74 mcg) ciclesonide nasal aerosol: ciclesonide nasal aerosol (74 mcg)
Overall Study
STARTED
42
47
Overall Study
COMPLETED
41
47
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Placebo: Placebo
Ciclesonide Nasal Aerosol
ciclesonide nasal aerosol (74 mcg) ciclesonide nasal aerosol: ciclesonide nasal aerosol (74 mcg)
Overall Study
Noncompliance with study drug
1
0

Baseline Characteristics

Safety Study of the Potential Inhibitory Effects of Ciclesonide Nasal Aerosol on the Hypothalamic-Pituitary-Adrenal Axis in Subjects 6-11 Years With Perennial Allergic Rhinitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol (74 mcg)
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Total
n=89 Participants
Total of all reporting groups
Age, Continuous
9.2 years
STANDARD_DEVIATION 1.74 • n=5 Participants
8.6 years
STANDARD_DEVIATION 1.65 • n=7 Participants
8.9 years
STANDARD_DEVIATION 1.70 • n=5 Participants
Age, Categorical
<=18 years
42 Participants
n=5 Participants
47 Participants
n=7 Participants
89 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
22 Participants
n=5 Participants
22 Participants
n=7 Participants
44 Participants
n=5 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants
25 Participants
n=7 Participants
45 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
11 Participants
n=5 Participants
8 Participants
n=7 Participants
19 Participants
n=5 Participants
Race (NIH/OMB)
White
29 Participants
n=5 Participants
35 Participants
n=7 Participants
64 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
15 Participants
n=5 Participants
17 Participants
n=7 Participants
32 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
27 Participants
n=5 Participants
30 Participants
n=7 Participants
57 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
42 participants
n=5 Participants
47 participants
n=7 Participants
89 participants
n=5 Participants

PRIMARY outcome

Timeframe: Week 0 and 6

Population: The Per Protocol (PP) population consisted of all ITT subjects who had sufficient blood sample collection at Visit 4/BL and Visit 7/End of Week 6 for serum cortisol measurements, completed the study on treatment medication and had no important protocol deviations (IPDs).

Area under the concentration-time curve from time 0 to 24 hours \[AUC(0-24h)\]. Timepoints at which data were collected: 0, 2, 4, 8, 12, 16, and 24 at week 0 and 6.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=46 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
The Change in Serum Cortisol Area Under the Curve (AUC) From Time 0 to 24 Hours (0-24), Calculated Using a Trapezoidal Rule, From Baseline to the End of the 6 Week Treatment Period
5.9 mcg•hour/dL
Standard Error 5.6
-1.7 mcg•hour/dL
Standard Error 5.2

SECONDARY outcome

Timeframe: weeks 0-6

Population: The PP population. Subjects with either missing baseline data or post dose data, or both were not included in the analysis

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=45 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Change From Baseline in Urinary Free Cortisol-Corrected for Urine Creatinine
1.4 mcg/g
Standard Error 2.9
3.3 mcg/g
Standard Error 2.7

SECONDARY outcome

Timeframe: weeks 0-6

Population: The PP population consisted of all ITT subjects who had sufficient blood sample collection at Visit 4/BL and Visit 7/End of Week 6 for serum cortisol measurements, completed the study on treatment medication and had no IPDs.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=45 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Change From Baseline in Urinary Free Cortisol-Uncorrected for Urine Creatinine
0.5 mcg/g
Standard Error 1.9
1.2 mcg/g
Standard Error 1.8

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Outcome measures

Outcome measures
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Number of Subjects Experiencing AEs
Any AE
19 participants
20 participants
Number of Subjects Experiencing AEs
Potentially related AE
6 participants
4 participants
Number of Subjects Experiencing AEs
Nasal (local) AEs
6 participants
5 participants
Number of Subjects Experiencing AEs
Discontinued study drug due to an AE
0 participants
0 participants
Number of Subjects Experiencing AEs
Severe AE
1 participants
0 participants
Number of Subjects Experiencing AEs
Serious AE
0 participants
0 participants
Number of Subjects Experiencing AEs
Death
0 participants
0 participants

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Outcome measures

Outcome measures
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Percentage of Subjects Experiencing AEs
Any AE
45.2 percentage of participants
42.6 percentage of participants
Percentage of Subjects Experiencing AEs
Potentially related AE
14.3 percentage of participants
8.5 percentage of participants
Percentage of Subjects Experiencing AEs
Nasal (local) AEs
14.3 percentage of participants
10.6 percentage of participants
Percentage of Subjects Experiencing AEs
Discontinued study drug due to an AE
0 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing AEs
Severe AE
2.4 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing AEs
Serious AE
0 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing AEs
Death
0 percentage of participants
0 percentage of participants

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Local Treatment-Emergent Adverse Events (ITT Population)

Outcome measures

Outcome measures
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Overall
6 participants
5 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Epistaxis
2 participants
1 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Mucosal erosion
1 participants
0 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Nasal discomfort
1 participants
1 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Postnasal drip
0 participants
1 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Rhinitis
1 participants
0 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Rhinorrhea
0 participants
1 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Traumatic hemorrhage
1 participants
0 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Upper respiratory tract infection
0 participants
1 participants
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Viral upper respiratory tract infection
2 participants
0 participants

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Local Treatment-Emergent Adverse Events (ITT Population)

Outcome measures

Outcome measures
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Viral upper respiratory tract infection
4.8 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Overall
14.3 percentage of participants
10.6 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Epistaxis
4.8 percentage of participants
2.1 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Mucosal erosion
2.4 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Nasal discomfort
2.4 percentage of participants
2.1 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Postnasal drip
0 percentage of participants
2.1 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Rhinitis
2.4 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Rhinorrhea
0 percentage of participants
2.1 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Traumatic hemorrhage
2.4 percentage of participants
0 percentage of participants
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Upper respiratory tract infection
0 percentage of participants
2.1 percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: PK Population: Subjects in the ITT population who completed the study on treatment medication and had assayed serum concentrations of ciclesonide and/or des ciclesonide. Descriptive statistics were presented for serum drug/metabolite concentrations and evaluable pharmacokinetic parameters.

Area under the concentration-time curve from time 0 to 24 hours. Collected at 0, 30 min, 60 min, 90 min, 2 hours (h), 4 h, 8 h, 12 h, 16 h, and 24h after dosing.

Outcome measures

Outcome measures
Measure
Placebo
n=47 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
AUC(0-24h)
Ciclesonide serum concentration
0.072 ng*hr/mL
Standard Deviation 0.261
AUC(0-24h)
Des-ciclesonide serum concentration
0.261 ng*hr/mL
Standard Deviation 0.139

SECONDARY outcome

Timeframe: Week 6

Population: PK Population: Subjects in the ITT population who completed the study on treatment medication and had assayed serum concentrations of ciclesonide and/or des ciclesonide. Descriptive statistics were presented for serum drug/metabolite concentrations and evaluable pharmacokinetic parameters.

Cmax (ng/mL) (PK Population)

Outcome measures

Outcome measures
Measure
Placebo
n=47 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Maximum Observed Concentration
Ciclesonide serum concentration
0.012 ng/mL
Standard Deviation 0.0009
Maximum Observed Concentration
Des-ciclesonide serum concentration
0.029 ng/mL
Standard Deviation 0.0169

SECONDARY outcome

Timeframe: Week 6

Population: PK Population: Subjects in the ITT population who completed the study on treatment medication and had assayed serum concentrations of ciclesonide and/or des ciclesonide. Descriptive statistics were presented for serum drug/metabolite concentrations and evaluable pharmacokinetic parameters.

tmax (hour) (PK Population)

Outcome measures

Outcome measures
Measure
Placebo
n=47 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Time to the Occurrence of Cmax
Ciclesonide serum concentration
1.146 Hour
Standard Deviation 0.700
Time to the Occurrence of Cmax
Des-ciclesonide serum concentration
2.200 Hour
Standard Deviation 1.330

SECONDARY outcome

Timeframe: Weeks 6

Population: PK Population: Subjects in the ITT population who completed the study on treatment medication and had assayed serum concentrations of ciclesonide and/or des ciclesonide. Descriptive statistics were presented for serum drug/metabolite concentrations and evaluable pharmacokinetic parameters.

Terminal half-life (t1/2) (hour)

Outcome measures

Outcome measures
Measure
Placebo
n=47 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Terminal Half Life (t1/2)
Ciclesonide serum concentration
8.194 Hour
Standard Deviation 12.448
Terminal Half Life (t1/2)
Des-ciclesonide serum concentration
11.727 Hour
Standard Deviation 5.864

SECONDARY outcome

Timeframe: Week 6

Population: PK Population: Subjects in the ITT population who completed the study on treatment medication and had assayed serum concentrations of ciclesonide and/or des ciclesonide. Descriptive statistics were presented for serum drug/metabolite concentrations and evaluable pharmacokinetic parameters.

CL/F liter per hour (L/hour) is the apparent clearance of the drug

Outcome measures

Outcome measures
Measure
Placebo
n=47 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Apparent Clearance of the Drug (CL/F)
Ciclesonide serum concentration
1222.4 L/hour
Standard Deviation 573.99
Apparent Clearance of the Drug (CL/F)
Des-ciclesonide serum concentration
317.8 L/hour
Standard Deviation 190.49

SECONDARY outcome

Timeframe: Week 6

Population: PK Population: Subjects in the ITT population who completed the study on treatment medication and had assayed serum concentrations of ciclesonide and/or des ciclesonide. Descriptive statistics were presented for serum drug/metabolite concentrations and evaluable pharmacokinetic parameters.

Vz/F Liters (L) is the apparent volume of distribution

Outcome measures

Outcome measures
Measure
Placebo
n=47 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Apparent Volume of Distribution (Vz/F)
Ciclesonide serum concentration
34831.4 L
Standard Deviation 35986.86
Apparent Volume of Distribution (Vz/F)
Des-ciclesonide serum concentration
6151.3 L
Standard Deviation 7999.78

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Outcome measures

Outcome measures
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Ratio (Percentage) of the Number of Correct Advances of the Dose Indicator to the Number of Expected Advances Based on Subject Self-report of Study Medication Administration Plus Extra Non-nasal Actuations
101.75 percentage of number of correct advances
Standard Deviation 9.647
100.73 percentage of number of correct advances
Standard Deviation 11.637

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Outcome measures

Outcome measures
Measure
Placebo
n=123 Devices
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=141 Devices
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Number of Devices With Actuation Consistency, Where Actuation Consistency is Defined as a Dose Indicator Count Within ± 20% of the Subject Self-report of Study Medication Administration
112 Devices
126 Devices

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

Outcome measures

Outcome measures
Measure
Placebo
n=123 Devices
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=141 Devices
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Percentage of Devices With Actuation Consistency, Where Actuation Consistency is Defined as a Dose Indicator Count Within ± 20% of the Subject Self-report of Study Medication Administration
91.1 percentage of devices
89.4 percentage of devices

SECONDARY outcome

Timeframe: weeks 0-6

Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.

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

Outcome measures

Outcome measures
Measure
Placebo
n=42 Participants
Placebo nasal aerosol administered once daily (1 actuation per nostril)
Ciclesonide Nasal Aerosol
n=47 Participants
Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril)
Change From Baseline in Averaged Daily Subject-reported AM and PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment
-0.7 units on a scale
Standard Deviation 1.65
-1.5 units on a scale
Standard Deviation 2.04

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Ciclesonide Nasal Aerosol

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Placebo
n=42 participants at risk
Placebo: Placebo
Ciclesonide Nasal Aerosol
n=47 participants at risk
ciclesonide nasal aerosol (74 mcg) ciclesonide nasal aerosol: ciclesonide nasal aerosol (74 mcg)
Nervous system disorders
Headache
2.4%
1/42 • Number of events 3 • 0-6 weeks
6.4%
3/47 • Number of events 4 • 0-6 weeks
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
9.5%
4/42 • Number of events 5 • 0-6 weeks
0.00%
0/47 • 0-6 weeks

Additional Information

Respiratory Medical Director

Sunovion

Phone: 866-503-6351

Results disclosure agreements

  • Principal investigator is a sponsor employee In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
  • Publication restrictions are in place

Restriction type: OTHER