Allergic Rhinitis
Conditions
Keywords
Allergic rhinitis
Brief summary
The purpose of this study is to compare the systemic des-ciclesonide exposure of OMNARIS™ (ciclesonide) nasal spray, ciclesonide HFA nasal aerosol, and orally inhaled ciclesonide HFA-metered-dose inhaler (MDI). The administration of the study medication will be as follows: three single doses, separated by a wash-out period. The study will provide further data on the safety and tolerability of ciclesonide.
Interventions
DRUGCiclesonide
Sponsors
Covis Pharma S.à.r.l.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Written informed consent and HIPAA * Body weight as indicate by a Body Mass Index (BMI) between ≥ 18 and ≤ 28 kg/m², and a body weight \>50 kg * General good health * Ability to use oral inhaler Main
Exclusion criteria
* Pregnancy, breast feeding, intention to become pregnant during the course of the study or lack of safe contraception in pre-menopausal women * Participation in any investigational drug trial within the 30 days before Screening Visit and thereafter * History or current clinically relevant allergies or idiosyncrasy to drugs or food * History of allergic reactions to any corticosteroids including ciclesonide or any excipients of the formulations * Any contraindication to nasally administered corticosteroids * History of a respiratory infection or disorder \[including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, flu, severe acute respiratory syndrome (SARS)\] within the 30 days before Screening Visit, or development of a respiratory infection during the Screening Period * History or current evidence of any other relevant allergic, cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, metabolic, neurological, psychiatric, or other disease within the last 2 years * Non-vaccinated exposure to or active infection with, chickenpox or measles within the 21 days preceding Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Systemic Exposure Measured by AUC, ng*hr/L, (Area Under the Serum Concentration) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 5min, 15min, 30min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h following drug administration. | The primary pharmacokinetics comparisons between treatments will be that of 300 mcg OMNARIS™ \[ciclesonide\] nasal spray and 300 mcg ciclesonide nasal HFA aerosol vs. 320 mcg orally inhaled ciclesonide as a reference. At prespecified timepoints, blood samples were obtained from subjects. It was anticipated that only a limited number of des-ciclesonide concentrations would exceed the lower limit of quantification (LLOQ) of 10 pg/mL for ciclesonide aqueous nasal spray. AUC for the aqueous nasal spray could not be determined due to the fact that there were too few analysis samples that produced values above the LLOQ. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Systemic Exposure Measured by Cmax, pg/mL, (Highest Concentration of Drug in the Blood) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 5min, 15min, 30min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h following drug administration. | The primary pharmacokinetics comparisons between treatments will be that of 300 mcg OMNARIS™ \[ciclesonide\] nasal spray and 300 mcg ciclesonide nasal HFA aerosol vs. 320 mcg orally inhaled ciclesonide as a reference. At prespecified timepoints, blood samples were obtained from subjects. The Cmax may be available only for a limited number of subjects. Thus the focus of statistical PK analysis will be on descriptive statistics. In particular, mean and median for Cmax will be calculated using data from subjects with Cmax above LLOQ (Lower Limit of Quantitation) and from all subjects with Cmax below LLOQ imputed by 0. |
Countries
United States
Participant flow
Pre-assignment details
This is a 3-period crossover study of 30 subjects total; There were three single dose treatment periods separated by a washout of 7-14 days.
Participants by arm
| Arm | Count |
|---|---|
| Ciclesonide Nasal Spray, Then Ciclesonide Nasal Aerosol, Then Ciclesonide HFA MDI Participants first received Ciclesonide 300 mcg intranasally via aqueous nasal spray. After a 7-14 days washout period, they then received Ciclesonide 300 mcg via HFA nasal aerosol. After another 7-14 days washout period, they then received Ciclesonide 320 mcg orally inhaled via HFA MDI. | 5 |
| Ciclesonide Nasal Aerosol, Then Ciclesonide HFA MDI, Then Ciclesonide Nasal Spray Participants first received Ciclesonide 300 mcg via HFA nasal aerosol. After a 7-14 days washout period, they then received Ciclesonide 320 mcg orally inhaled via HFA MDI. After another 7-14 days washout period, they then received Ciclesonide 300 mcg intranasally via aqueous nasal spray. | 5 |
| Ciclesonide HFA MDI, Then Ciclesonide Nasal Spray, Then Ciclesonide Nasal Aerosol Participants first received Ciclesonide 320 mcg orally inhaled via HFA MDI. After a 7-14 days washout period, they then received Ciclesonide 300 mcg intranasally via aqueous nasal spray. After another 7-14 days washout period, they then received Ciclesonide 300 mcg via HFA nasal aerosol. | 5 |
| Ciclesonide Nasal Spray, Then Ciclesonide HFA MDI, Then Ciclesonide Nasal Aerosol Participants first received Ciclesonide 300 mcg intranasally via aqueous nasal spray. After a 7-14 days washout period, they then received Ciclesonide 320 mcg orally inhaled via HFA MDI. After another 7-14 days washout period, they then received Ciclesonide 300 mcg via HFA nasal aerosol. | 5 |
| Ciclesonide Nasal Aerosol, Then Ciclesonide Nasal Spray, Then Ciclesonide HFA MDI Participants first received Ciclesonide 300 mcg via HFA nasal aerosol. After a 7-14 days washout period, they then received Ciclesonide 300 mcg intranasally via aqueous nasal spray. After another 7-14 days washout period, they then received Ciclesonide 320 mcg orally inhaled via HFA MDI. | 5 |
| Ciclesonide HFA MDI, Then Ciclesonide Nasal Aerosol, Then Ciclesonide Nasal Spray Participants first received Ciclesonide 320 mcg orally inhaled via HFA MDI. After a 7-14 days washout period, they then received they then received Ciclesonide 300 mcg via HFA nasal aerosol. After another 7-14 days washout period, Ciclesonide 300 mcg intranasally via aqueous nasal spray. | 5 |
| Total | 30 |
Baseline characteristics
| Characteristic | Ciclesonide Nasal Aerosol, Then Ciclesonide HFA MDI, Then Ciclesonide Nasal Spray | Ciclesonide HFA MDI, Then Ciclesonide Nasal Spray, Then Ciclesonide Nasal Aerosol | Ciclesonide Nasal Spray, Then Ciclesonide HFA MDI, Then Ciclesonide Nasal Aerosol | Ciclesonide Nasal Spray, Then Ciclesonide Nasal Aerosol, Then Ciclesonide HFA MDI | Ciclesonide Nasal Aerosol, Then Ciclesonide Nasal Spray, Then Ciclesonide HFA MDI | Ciclesonide HFA MDI, Then Ciclesonide Nasal Aerosol, Then Ciclesonide Nasal Spray | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 30 Participants |
| Age, Continuous | 38.4 years STANDARD_DEVIATION 4.75 | 38.2 years STANDARD_DEVIATION 13.39 | 26.8 years STANDARD_DEVIATION 7.24 | 40.2 years STANDARD_DEVIATION 13.39 | 38 years STANDARD_DEVIATION 14.09 | 33.8 years STANDARD_DEVIATION 8.58 | 35.90 years STANDARD_DEVIATION 11.95 |
| Region of Enrollment United States | 5 participants | 5 participants | 5 participants | 5 participants | 5 participants | 5 participants | 30 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 19 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 4 / 29 | 9 / 29 | 3 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 | 0 / 29 |
Outcome results
Primary
Comparison of Systemic Exposure Measured by AUC, ng*hr/L, (Area Under the Serum Concentration) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide.
The primary pharmacokinetics comparisons between treatments will be that of 300 mcg OMNARIS™ \[ciclesonide\] nasal spray and 300 mcg ciclesonide nasal HFA aerosol vs. 320 mcg orally inhaled ciclesonide as a reference. At prespecified timepoints, blood samples were obtained from subjects. It was anticipated that only a limited number of des-ciclesonide concentrations would exceed the lower limit of quantification (LLOQ) of 10 pg/mL for ciclesonide aqueous nasal spray. AUC for the aqueous nasal spray could not be determined due to the fact that there were too few analysis samples that produced values above the LLOQ.
Time frame: 5min, 15min, 30min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h following drug administration.
Population: A total of 30 healthy volunteers were randomized in the study. Thirty were included in the ITT population; 29 subjects were included in the PP population. All 30 were included in the safety population. A subject was completely excluded from PP analyses as a major violation (common cold) and also due to the number of scheduled blood sample collections that could not be obtained subsequent to this subject's request for premature termination from the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciclesonide Nasal Spray | Comparison of Systemic Exposure Measured by AUC, ng*hr/L, (Area Under the Serum Concentration) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | NA ng*hr/L |
| Ciclesonide Nasal Aerosol | Comparison of Systemic Exposure Measured by AUC, ng*hr/L, (Area Under the Serum Concentration) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 403.7 ng*hr/L |
| Ciclesonide HFA MDI | Comparison of Systemic Exposure Measured by AUC, ng*hr/L, (Area Under the Serum Concentration) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 2762 ng*hr/L |
Secondary
Comparison of Systemic Exposure Measured by Cmax, pg/mL, (Highest Concentration of Drug in the Blood) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide.
The primary pharmacokinetics comparisons between treatments will be that of 300 mcg OMNARIS™ \[ciclesonide\] nasal spray and 300 mcg ciclesonide nasal HFA aerosol vs. 320 mcg orally inhaled ciclesonide as a reference. At prespecified timepoints, blood samples were obtained from subjects. The Cmax may be available only for a limited number of subjects. Thus the focus of statistical PK analysis will be on descriptive statistics. In particular, mean and median for Cmax will be calculated using data from subjects with Cmax above LLOQ (Lower Limit of Quantitation) and from all subjects with Cmax below LLOQ imputed by 0.
Time frame: 5min, 15min, 30min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h following drug administration.
Population: A total of 30 healthy volunteers were randomized in the study. Thirty were included in the ITT population; 29 subjects were included in the PP population. All 30 were included in the safety population. A subject was completely excluded from PP analyses as a major violation (common cold) and also due to the number of scheduled blood sample collections that could not be obtained subsequent to this subject's request for premature termination from the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciclesonide Nasal Spray | Comparison of Systemic Exposure Measured by Cmax, pg/mL, (Highest Concentration of Drug in the Blood) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 20.05 pg/mL |
| Ciclesonide Nasal Aerosol | Comparison of Systemic Exposure Measured by Cmax, pg/mL, (Highest Concentration of Drug in the Blood) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 59.0 pg/mL |
| Ciclesonide HFA MDI | Comparison of Systemic Exposure Measured by Cmax, pg/mL, (Highest Concentration of Drug in the Blood) of Des-ciclesonide With Ciclesonide Nasal Spray, and Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide. | 602.0 pg/mL |