PAR, Perennial Allergic Rhinitis
Conditions
Keywords
Perennial Allergic Rhinitis, PAR
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, safety study of the effects of ciclesonide nasal aerosol (74 mcg) on the HPA axis when administered once daily to male and premenarchal female subjects 6 to 11 years of age with a diagnosis of PAR.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, safety study of the effects of ciclesonide nasal aerosol (74 mcg) on the HPA axis when administered once daily to male and premenarchal female subjects 6 to 11 years of age with a diagnosis of PAR. The study requires that subjects be domiciled during two 24- to 36-hour time periods for sample collection for serum and urinary free cortisol measurements, as well as PK evaluations (single \[predose\] time point during the first domiciled period, and 24-hour sampling during the second domiciled period).
Interventions
ciclesonide nasal aerosol (74 mcg)
DRUGPlacebo
Placebo
Sponsors
Sumitomo Pharma America, Inc.
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
No
Inclusion criteria
* Gives written informed consent (parent/legal guardian) and assent (when appropriate, 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 and ≥ 20 kg at the screening visit. * 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 PAR to a relevant perennial allergen (house dust mites, cockroaches, molds, animal dander) for a minimum of one year 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. * Has a demonstrated sensitivity to at least one allergen known to induce PAR (house dust mites, cockroaches, molds, and animal dander) based on a documented result with a standard skin-prick test either within one year prior to the screening visit or performed at the screening visit. A positive test is defined as a wheal diameter at least 3 mm larger than the negative control wheal for the skin-prick test. The subject's positive allergen test must be consistent with the medical history of of PAR, and the allergen must be present in the subject's environment throughout the study.
Exclusion criteria
* Has a 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 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 a history of adrenal insufficiency. * 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. * Is expecting to use any disallowed concomitant medications during the treatment period. * Is, in the investigator's judgment, having a seasonal exacerbation at the time of the screening visit. * 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. * Has experienced significant blood loss within 60 days or loss of plasma within 72 hours prior to the screening visit or intends to undergo elective surgery within 30 days following end of study. * Is a child or immediate relative of any clinical investigator or site personnel, even those who are not directly involved in this study. * Resides in the same household as another subject who is participating in this study at the same time. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 0 and 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Urinary Free Cortisol-Uncorrected for Urine Creatinine | weeks 0-6 | — |
| Number of Subjects Experiencing AEs | weeks 0-6 | — |
| Percentage of Subjects Experiencing AEs | weeks 0-6 | — |
| Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | weeks 0-6 | Local Treatment-Emergent Adverse Events (ITT Population) |
| Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | weeks 0-6 | Local Treatment-Emergent Adverse Events (ITT Population) |
| AUC(0-24h) | Week 6 | 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. |
| Maximum Observed Concentration | Week 6 | Cmax (ng/mL) (PK Population) |
| Change From Baseline in Urinary Free Cortisol-Corrected for Urine Creatinine | weeks 0-6 | — |
| Terminal Half Life (t1/2) | Weeks 6 | Terminal half-life (t1/2) (hour) |
| Apparent Clearance of the Drug (CL/F) | Week 6 | CL/F liter per hour (L/hour) is the apparent clearance of the drug |
| Apparent Volume of Distribution (Vz/F) | Week 6 | Vz/F Liters (L) is the apparent volume of distribution |
| 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 | weeks 0-6 | — |
| 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 | weeks 0-6 | — |
| 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 | weeks 0-6 | — |
| Change From Baseline in Averaged Daily Subject-reported AM and PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment | weeks 0-6 | TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual 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 |
| Time to the Occurrence of Cmax | Week 6 | tmax (hour) (PK Population) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo nasal aerosol administered once daily (1 actuation per nostril) | 42 |
| Ciclesonide Nasal Aerosol (74 mcg) Ciclesonide nasal aerosol 74 mcg administered once daily (1 actuation of 37 mcg per nostril) | 47 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Noncompliance with study drug | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Ciclesonide Nasal Aerosol (74 mcg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 42 Participants | 47 Participants | 89 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 9.2 years STANDARD_DEVIATION 1.74 | 8.6 years STANDARD_DEVIATION 1.65 | 8.9 years STANDARD_DEVIATION 1.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 17 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 30 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 8 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 35 Participants | 64 Participants |
| Region of Enrollment United States | 42 participants | 47 participants | 89 participants |
| Sex: Female, Male Female | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Male | 20 Participants | 25 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 42 | 3 / 47 |
| serious Total, serious adverse events | 0 / 42 | 0 / 47 |
Outcome results
Primary
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
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.
Time frame: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ciclesonide Nasal Aerosol | 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 | -1.7 mcg•hour/dL | Standard Error 5.2 |
Comparison: 35 subjects per arm would have ≥90% power to demonstrate that the upper bound of a two-sided 95% confidence interval (equivalent to the upper bound of a one-sided 97.5% confidence interval) of the difference of placebo minus ciclesonide nasal aerosol would be less than 20% of the baseline value of 175 mcg•h/dL or a noninferiority limit of 35 mcg•h/dL assuming a SD of 40 and a one-sided α of 0.025. A total of 40 subjects will be randomly assigned to ensure 35 subjects complete the study per arm.95% CI: [-7.4, 22.6]ANCOVA
Secondary
Apparent Clearance of the Drug (CL/F)
CL/F liter per hour (L/hour) is the apparent clearance of the drug
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apparent Clearance of the Drug (CL/F) | Ciclesonide serum concentration | 1222.4 L/hour | Standard Deviation 573.99 |
| Placebo | Apparent Clearance of the Drug (CL/F) | Des-ciclesonide serum concentration | 317.8 L/hour | Standard Deviation 190.49 |
Secondary
Apparent Volume of Distribution (Vz/F)
Vz/F Liters (L) is the apparent volume of distribution
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apparent Volume of Distribution (Vz/F) | Ciclesonide serum concentration | 34831.4 L | Standard Deviation 35986.86 |
| Placebo | Apparent Volume of Distribution (Vz/F) | Des-ciclesonide serum concentration | 6151.3 L | Standard Deviation 7999.78 |
Secondary
AUC(0-24h)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC(0-24h) | Ciclesonide serum concentration | 0.072 ng*hr/mL | Standard Deviation 0.261 |
| Placebo | AUC(0-24h) | Des-ciclesonide serum concentration | 0.261 ng*hr/mL | Standard Deviation 0.139 |
Secondary
Change From Baseline in Averaged Daily Subject-reported AM and PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment
TNSS is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent 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
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ciclesonide Nasal Aerosol | Change From Baseline in Averaged Daily Subject-reported AM and PM Reflective TNSS Averaged Over the 6 Weeks of Double-blind Treatment | -1.5 units on a scale | Standard Deviation 2.04 |
Secondary
Change From Baseline in Urinary Free Cortisol-Corrected for Urine Creatinine
Time frame: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urinary Free Cortisol-Corrected for Urine Creatinine | 1.4 mcg/g | Standard Error 2.9 |
| Ciclesonide Nasal Aerosol | Change From Baseline in Urinary Free Cortisol-Corrected for Urine Creatinine | 3.3 mcg/g | Standard Error 2.7 |
Secondary
Change From Baseline in Urinary Free Cortisol-Uncorrected for Urine Creatinine
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urinary Free Cortisol-Uncorrected for Urine Creatinine | 0.5 mcg/g | Standard Error 1.9 |
| Ciclesonide Nasal Aerosol | Change From Baseline in Urinary Free Cortisol-Uncorrected for Urine Creatinine | 1.2 mcg/g | Standard Error 1.8 |
Secondary
Maximum Observed Concentration
Cmax (ng/mL) (PK Population)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Concentration | Ciclesonide serum concentration | 0.012 ng/mL | Standard Deviation 0.0009 |
| Placebo | Maximum Observed Concentration | Des-ciclesonide serum concentration | 0.029 ng/mL | Standard Deviation 0.0169 |
Secondary
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
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 |
| Ciclesonide Nasal Aerosol | 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 | 126 Devices |
Secondary
Number of Subjects Experiencing AEs
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Subjects Experiencing AEs | Discontinued study drug due to an AE | 0 participants |
| Placebo | Number of Subjects Experiencing AEs | Any AE | 19 participants |
| Placebo | Number of Subjects Experiencing AEs | Severe AE | 1 participants |
| Placebo | Number of Subjects Experiencing AEs | Nasal (local) AEs | 6 participants |
| Placebo | Number of Subjects Experiencing AEs | Serious AE | 0 participants |
| Placebo | Number of Subjects Experiencing AEs | Death | 0 participants |
| Placebo | Number of Subjects Experiencing AEs | Potentially related AE | 6 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Death | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Any AE | 20 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Potentially related AE | 4 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Nasal (local) AEs | 5 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Discontinued study drug due to an AE | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Severe AE | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing AEs | Serious AE | 0 participants |
Secondary
Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Local Treatment-Emergent Adverse Events (ITT Population)
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Overall | 6 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Epistaxis | 2 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Mucosal erosion | 1 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Nasal discomfort | 1 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Postnasal drip | 0 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinitis | 1 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinorrhea | 0 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Traumatic hemorrhage | 1 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Upper respiratory tract infection | 0 participants |
| Placebo | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Viral upper respiratory tract infection | 2 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Traumatic hemorrhage | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Overall | 5 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinitis | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Epistaxis | 1 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Viral upper respiratory tract infection | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Mucosal erosion | 0 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinorrhea | 1 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Nasal discomfort | 1 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Upper respiratory tract infection | 1 participants |
| Ciclesonide Nasal Aerosol | Number of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Postnasal drip | 1 participants |
Secondary
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
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 |
| Ciclesonide Nasal Aerosol | 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 | 89.4 percentage of devices |
Secondary
Percentage of Subjects Experiencing AEs
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Subjects Experiencing AEs | Nasal (local) AEs | 14.3 percentage of participants |
| Placebo | Percentage of Subjects Experiencing AEs | Severe AE | 2.4 percentage of participants |
| Placebo | Percentage of Subjects Experiencing AEs | Potentially related AE | 14.3 percentage of participants |
| Placebo | Percentage of Subjects Experiencing AEs | Serious AE | 0 percentage of participants |
| Placebo | Percentage of Subjects Experiencing AEs | Discontinued study drug due to an AE | 0 percentage of participants |
| Placebo | Percentage of Subjects Experiencing AEs | Death | 0 percentage of participants |
| Placebo | Percentage of Subjects Experiencing AEs | Any AE | 45.2 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Death | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Any AE | 42.6 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Potentially related AE | 8.5 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Nasal (local) AEs | 10.6 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Discontinued study drug due to an AE | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Severe AE | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing AEs | Serious AE | 0 percentage of participants |
Secondary
Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation.
Local Treatment-Emergent Adverse Events (ITT Population)
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Overall | 14.3 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Epistaxis | 4.8 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Mucosal erosion | 2.4 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Nasal discomfort | 2.4 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Postnasal drip | 0 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinitis | 2.4 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinorrhea | 0 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Traumatic hemorrhage | 2.4 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Upper respiratory tract infection | 0 percentage of participants |
| Placebo | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Viral upper respiratory tract infection | 4.8 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Traumatic hemorrhage | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Overall | 10.6 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinitis | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Epistaxis | 2.1 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Viral upper respiratory tract infection | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Mucosal erosion | 0 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Rhinorrhea | 2.1 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Nasal discomfort | 2.1 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Upper respiratory tract infection | 2.1 percentage of participants |
| Ciclesonide Nasal Aerosol | Percentage of Subjects Experiencing Nasal AEs, Including Epistaxis, Nasal Ulceration, and Nasal Perforation. | Postnasal drip | 2.1 percentage of participants |
Secondary
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
Time frame: weeks 0-6
Population: Intent-to-treat (ITT) Population: All randomized subjects who received at least 1 dose of double blind study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ciclesonide Nasal Aerosol | 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 | 100.73 percentage of number of correct advances | Standard Deviation 11.637 |
Secondary
Terminal Half Life (t1/2)
Terminal half-life (t1/2) (hour)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Terminal Half Life (t1/2) | Ciclesonide serum concentration | 8.194 Hour | Standard Deviation 12.448 |
| Placebo | Terminal Half Life (t1/2) | Des-ciclesonide serum concentration | 11.727 Hour | Standard Deviation 5.864 |
Secondary
Time to the Occurrence of Cmax
tmax (hour) (PK Population)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time to the Occurrence of Cmax | Ciclesonide serum concentration | 1.146 Hour | Standard Deviation 0.7 |
| Placebo | Time to the Occurrence of Cmax | Des-ciclesonide serum concentration | 2.200 Hour | Standard Deviation 1.33 |