Allergic Rhinitis
Conditions
Keywords
Pediatric Subjects
Brief summary
The purpose of this study is to compare the effect of 6 weeks of treatment with beclomethasone dipropionate (BDP) nasal aerosol versus placebo on HPA-axis function, as assessed by 24-hour serum cortisol weighted mean, and to evaluate the safety and tolerability of BDP nasal aerosol, in subjects 6 to 11 years of age with perennial allergic rhinitis.
Interventions
DRUGBDP
Beclomethasone dipropionate (BDP) 80 mcg/day (40 mcg/spray, 1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.
DRUGPlacebo
Placebo (1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.
Sponsors
Teva Branded Pharmaceutical Products R&D, 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
* Informed consent/(assent - if applicable) * Male or female subjects 6-11 years of age * General good health * A documented history of PAR to a relevant perennial allergen for a minimum of 12 months * Other criteria apply
Exclusion criteria
* Pregnancy, nursing, or plans to become pregnant or donate gametes * Participation in any investigational drug study within the 30 days preceding the Screening Visit 1 (SV1) * Previous participation in a BDP nasal aerosol study as a randomized subject * A known hypersensitivity to any corticosteroid or any of the excipients in the study medication formulation * History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations * History of a respiratory infection or disorder within the 14 days preceding the Screening Visit 1 (SV1) * Use of any prohibited concomitant medications within the prescribed (per protocol) withdrawal periods prior to the Screening Visit 1 (SV1) * Other criteria apply * Current smoker or current user of tobacco products at any time during the study; history of smoking or use of tobacco products within the past year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Expressed As A Ratio) In 24-Hr Serum Cortisol Weighted Mean Following 6 Weeks Of Treatment | Baseline (Day 1, -24, -22, -20, -16, -12, -8, and 0 hours prior to study medication), End of Treatment (Day 43, (Immediately prior to study medication administration (Hour 0) and at 2, 4, 8, 12, 16, and 24 hours after study medication administration) | The serum cortisol weighted mean (0-t), calculated by dividing the area under the concentration-time curve (AUC) from time zero to the time of the last measurable value over the 24-hour period by the sample collection time interval, was determined for each participant at baseline and Week 6, and the ratio of Week 6 over baseline was derived. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration) | Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics. |
| Maximum Plasma Concentration (Cmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration) | Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics. |
| Time to Reach Maximum Plasma Concentration (Tmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration) | Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics. |
| Terminal Elimination Rate Constant (λz ) for Beclomethasone-17-monopropionate (17-BMP) | Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration) | Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics. |
| Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-t ) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration) | Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics. |
| Participants With Treatment-Emergent Adverse Events (AEs) | Day 1- week 10 | The intensity or severity of the AE was characterized as mild (AE which is easily tolerated), moderate (AE sufficiently discomforting to interfere with daily activity) or severe (AE which prevents normal daily activities). The causal relationship was characterized as not related (no reasonable possibility that the AE was caused by or attributed to the investigational product) or related reasonable possibility that the AE was caused by or attributed to the investigational product / a causal relationship cannot be ruled out). An SAE was defined as an AE that resulted in any of the following: * Death * Life-threatening * Required hospitalization or prolonged existing hospitalization * Persistent or significant disability or incapacity * A congenital abnormality or birth defect * An important medical event which required medical intervention to prevent any of the above outcomes. |
| Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Screening (Day -21 to -7), End of Study (Day 42) | Shifting to 'High' refers to starting the study within normal range and being outside the high-end of normal by end of study. Conversely, shifting to 'Low' refers to starting the study within normal range and being outside the low-end of normal by end of study. MCHC = mean corpuscular hemoglobin concentration MCV = mean corpuscular volume, or mean cell volume MCH = mean corpuscular hemoglobin or mean cell hemoglobin |
| Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Screening (Day -21 to -7), End of Study (Day 42) | Shifting to 'High' refers to starting the study within normal range and being outside the high-end of normal by end of study. Conversely, shifting to 'Low' refers to starting the study within normal range and being outside the low-end of normal by end of study. BUN = blood urea nitrogen AST = aspartate transaminase ALT = alanine transaminase GGT = gamma-glutamyl transpeptidase |
| Terminal Elimination Half-life (t1/2) for Beclomethasone-17-monopropionate (17-BMP) | Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration) | Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics. |
Countries
United States
Participant flow
Pre-assignment details
A total of 110 subjects were screened. Participants were randomly assigned to either BDP nasal aerosol (80 mcg/day) or placebo nasal aerosol in a 2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| BDP Nasal Aerosol 80 mcg/Day BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 42 day (6 week) Treatment Period. | 66 |
| Placebo Nasal Aerosol Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 42 day (6 week) Treatment Period. | 31 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | BDP Nasal Aerosol 80 mcg/Day | Placebo Nasal Aerosol | Total |
|---|---|---|---|
| Age, Continuous | 9.2 years STANDARD_DEVIATION 1.54 | 8.5 years STANDARD_DEVIATION 1.65 | 9.0 years STANDARD_DEVIATION 1.6 |
| Body Mass Index | 18.8 kg/m^2 STANDARD_DEVIATION 4.01 | 18.2 kg/m^2 STANDARD_DEVIATION 3.66 | 18.6 kg/m^2 STANDARD_DEVIATION 3.89 |
| Race/Ethnicity, Customized Black | 17 participants | 6 participants | 23 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 16 participants | 10 participants | 26 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 50 participants | 21 participants | 71 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 48 participants | 24 participants | 72 participants |
| Sex: Female, Male Female | 31 Participants | 20 Participants | 51 Participants |
| Sex: Female, Male Male | 35 Participants | 11 Participants | 46 Participants |
| Weight | 37.5 kg STANDARD_DEVIATION 12.84 | 34.9 kg STANDARD_DEVIATION 12.89 | 36.7 kg STANDARD_DEVIATION 12.85 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 67 | 6 / 32 |
| serious Total, serious adverse events | 0 / 67 | 0 / 32 |
Outcome results
Primary
Change From Baseline (Expressed As A Ratio) In 24-Hr Serum Cortisol Weighted Mean Following 6 Weeks Of Treatment
The serum cortisol weighted mean (0-t), calculated by dividing the area under the concentration-time curve (AUC) from time zero to the time of the last measurable value over the 24-hour period by the sample collection time interval, was determined for each participant at baseline and Week 6, and the ratio of Week 6 over baseline was derived.
Time frame: Baseline (Day 1, -24, -22, -20, -16, -12, -8, and 0 hours prior to study medication), End of Treatment (Day 43, (Immediately prior to study medication administration (Hour 0) and at 2, 4, 8, 12, 16, and 24 hours after study medication administration)
Population: Per protocol (PP) population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Change From Baseline (Expressed As A Ratio) In 24-Hr Serum Cortisol Weighted Mean Following 6 Weeks Of Treatment | 1.04 ratio | Standard Error 1.037 |
| Placebo Nasal Aerosol | Change From Baseline (Expressed As A Ratio) In 24-Hr Serum Cortisol Weighted Mean Following 6 Weeks Of Treatment | 1.10 ratio | Standard Error 1.053 |
Comparison: The standard deviation of the logarithmically transformed data on the change from baseline (expressed as a ratio) in 24-hr serum cortisol weighted mean is assumed to be 0.30. Using this standard deviation, 90 subjects (approximately 60 and 30 subjects in the BDP Nasal Aerosol and placebo groups, respectively) will yield approximately 90% power to demonstrate non-inferiority between BDP Nasal Aerosol and placebo, if there is no true difference between treatment groups.95% CI: [0.81, 1.03]
Secondary
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics.
Time frame: Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration)
Population: Per protocol population of participants administered BDP nasal aerosol 80 mcg/day. Plasma BDP concentrations were generally low and were only measurable over a short period of time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 619.06 h*pg/mL | Standard Deviation 416.035 |
| Placebo Nasal Aerosol | Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 200.80 h*pg/mL | Standard Deviation 69.939 |
Secondary
Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-t ) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics.
Time frame: Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration)
Population: Per protocol population of participants administered BDP nasal aerosol 80 mcg/day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-t ) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 573.81 h*pg/mL | Standard Deviation 508.727 |
| Placebo Nasal Aerosol | Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-t ) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 45.60 h*pg/mL | Standard Deviation 59.037 |
Secondary
Maximum Plasma Concentration (Cmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics.
Time frame: Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration)
Population: Per protocol population of participants administered BDP nasal aerosol 80 mcg/day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Maximum Plasma Concentration (Cmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 142.68 pg/mL | Standard Deviation 77.728 |
| Placebo Nasal Aerosol | Maximum Plasma Concentration (Cmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 44.65 pg/mL | Standard Deviation 36.454 |
Secondary
Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study
Shifting to 'High' refers to starting the study within normal range and being outside the high-end of normal by end of study. Conversely, shifting to 'Low' refers to starting the study within normal range and being outside the low-end of normal by end of study. MCHC = mean corpuscular hemoglobin concentration MCV = mean corpuscular volume, or mean cell volume MCH = mean corpuscular hemoglobin or mean cell hemoglobin
Time frame: Screening (Day -21 to -7), End of Study (Day 42)
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Basophils (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | White blood cells (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCH (pg) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Segmented neutrophils (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Platelets (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Red blood cells (10^12/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Monocytes (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hemaglobin (g/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCHC (g/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Neutrophils (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Lymphocytes (10^9/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Eosinsphils (10^9/L) | 2 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCV (FL) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hematocrit (l/l) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Lymphocytes (10^9/L) | 1 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hemaglobin (g/L) | 1 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hematocrit (l/l) | 4 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCHC (g/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCV (FL) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCH (pg) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Red blood cells (10^12/L) | 3 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Platelets (10^9/L) | 1 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | White blood cells (10^9/L) | 9 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Basophils (10^9/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Eosinsphils (10^9/L) | 8 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Monocytes (10^9/L) | 10 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Neutrophils (10^9/L) | 8 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Segmented neutrophils (10^9/L) | 8 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Lymphocytes (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Neutrophils (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hematocrit (l/l) | 1 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCV (FL) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Monocytes (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hemaglobin (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Eosinsphils (10^9/L) | 3 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | White blood cells (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Red blood cells (10^12/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCHC (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCH (pg) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Segmented neutrophils (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Platelets (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Basophils (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Platelets (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | White blood cells (10^9/L) | 2 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Neutrophils (10^9/L) | 4 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Basophils (10^9/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCHC (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Eosinsphils (10^9/L) | 2 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hematocrit (l/l) | 2 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Lymphocytes (10^9/L) | 1 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Segmented neutrophils (10^9/L) | 4 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Monocytes (10^9/L) | 5 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCH (pg) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Hemaglobin (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | Red blood cells (10^12/L) | 2 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study | MCV (FL) | 0 participants |
Secondary
Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study
Shifting to 'High' refers to starting the study within normal range and being outside the high-end of normal by end of study. Conversely, shifting to 'Low' refers to starting the study within normal range and being outside the low-end of normal by end of study. BUN = blood urea nitrogen AST = aspartate transaminase ALT = alanine transaminase GGT = gamma-glutamyl transpeptidase
Time frame: Screening (Day -21 to -7), End of Study (Day 42)
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Chloride (mmol/L) | 2 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | ALT (u/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Albumin (g/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total bilirubin (micromol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Bicarbonate (mmol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Sodium (mmol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Uric acid (micromol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Glucose (mmol/L) | 1 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Alkaline phosphatase (u/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | AST (u/L) | 1 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Lactate dehydrogenase (u/L) | 1 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | BUN (mmol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Potassium (mmol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Phosphorus (mmol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | GGT (u/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Creatinine (micromol/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total protein (g/L) | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Calcium (mmol/L) | 1 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | ALT (u/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Phosphorus (mmol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total protein (g/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Sodium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Uric acid (micromol/L) | 1 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Lactate dehydrogenase (u/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Potassium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total bilirubin (micromol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Chloride (mmol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Albumin (g/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Bicarbonate (mmol/L) | 8 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Calcium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Glucose (mmol/L) | 1 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | GGT (u/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | BUN (mmol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | AST (u/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Creatinine (micromol/L) | 0 participants |
| Placebo Nasal Aerosol | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Alkaline phosphatase (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | GGT (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Calcium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Albumin (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Sodium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Potassium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Chloride (mmol/L) | 1 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Bicarbonate (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Glucose (mmol/L) | 1 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | BUN (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Creatinine (micromol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Phosphorus (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total protein (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Uric acid (micromol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | AST (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | ALT (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Alkaline phosphatase (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total bilirubin (micromol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to High | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Lactate dehydrogenase (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Sodium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | ALT (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Phosphorus (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Creatinine (micromol/L) | 1 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Calcium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Alkaline phosphatase (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | BUN (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Glucose (mmol/L) | 2 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Bicarbonate (mmol/L) | 3 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | GGT (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Chloride (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Potassium (mmol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Albumin (g/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Lactate dehydrogenase (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Uric acid (micromol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total bilirubin (micromol/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | AST (u/L) | 0 participants |
| Placebo Nasal Aerosol - Shift to Low | Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study | Total protein (g/L) | 0 participants |
Secondary
Participants With Treatment-Emergent Adverse Events (AEs)
The intensity or severity of the AE was characterized as mild (AE which is easily tolerated), moderate (AE sufficiently discomforting to interfere with daily activity) or severe (AE which prevents normal daily activities). The causal relationship was characterized as not related (no reasonable possibility that the AE was caused by or attributed to the investigational product) or related reasonable possibility that the AE was caused by or attributed to the investigational product / a causal relationship cannot be ruled out). An SAE was defined as an AE that resulted in any of the following: * Death * Life-threatening * Required hospitalization or prolonged existing hospitalization * Persistent or significant disability or incapacity * A congenital abnormality or birth defect * An important medical event which required medical intervention to prevent any of the above outcomes.
Time frame: Day 1- week 10
Population: Safety population which included all randomized participants who received at least one dose of randomized study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Participants With Treatment-Emergent Adverse Events (AEs) | Withdrawn due to AEs | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Treatment-Emergent Adverse Events (AEs) | Treatment-related AEs | 2 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Treatment-Emergent Adverse Events (AEs) | Severe AEs | 2 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Treatment-Emergent Adverse Events (AEs) | >=1 SAEs | 0 participants |
| BDP Nasal Aerosol 80 mcg/Day | Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AEs | 22 participants |
| Placebo Nasal Aerosol | Participants With Treatment-Emergent Adverse Events (AEs) | >=1 SAEs | 0 participants |
| Placebo Nasal Aerosol | Participants With Treatment-Emergent Adverse Events (AEs) | >=1 AEs | 13 participants |
| Placebo Nasal Aerosol | Participants With Treatment-Emergent Adverse Events (AEs) | Withdrawn due to AEs | 0 participants |
| Placebo Nasal Aerosol | Participants With Treatment-Emergent Adverse Events (AEs) | Severe AEs | 1 participants |
| Placebo Nasal Aerosol | Participants With Treatment-Emergent Adverse Events (AEs) | Treatment-related AEs | 1 participants |
Secondary
Terminal Elimination Half-life (t1/2) for Beclomethasone-17-monopropionate (17-BMP)
Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics.
Time frame: Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration)
Population: Per protocol population of participants administered BDP nasal aerosol 80 mcg/day. Due to the short duration of measurable BDP concentrations in plasma, t1/2 for BDP could not be estimated for any participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Terminal Elimination Half-life (t1/2) for Beclomethasone-17-monopropionate (17-BMP) | 3.10 hours | Standard Deviation 2.518 |
Secondary
Terminal Elimination Rate Constant (λz ) for Beclomethasone-17-monopropionate (17-BMP)
Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics.
Time frame: Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration)
Population: Per protocol population of participants administered BDP nasal aerosol 80 mcg/day. Due to the short duration of measurable BDP concentrations in plasma, λz for BDP could not be estimated for any participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Terminal Elimination Rate Constant (λz ) for Beclomethasone-17-monopropionate (17-BMP) | 0.31 1/hour | Standard Deviation 0.151 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Beclomethasone-17-monopropionate (17-BMP) is the active metabolite of BDP. Plasma concentrations of 17-BMP or BDP that were below the lower-limit-of-quantitation (LLOQ), 20 or 10 pg/mL, respectively, were assigned a zero value when calculating descriptive statistics.
Time frame: Day 42 (Predose (within 30 minutes prior to dose administration) and at 0.25 (15 min), 0.5 (30 min), 1, 1.5, 3, 6, 12, and 24 hours after final study medication administration)
Population: Per protocol population of participants administered BDP nasal aerosol 80 mcg/day. Plasma BDP concentrations were generally low and were only measurable over a short period of time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDP Nasal Aerosol 80 mcg/Day | Time to Reach Maximum Plasma Concentration (Tmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 1.15 hours | Standard Deviation 1.189 |
| Placebo Nasal Aerosol | Time to Reach Maximum Plasma Concentration (Tmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP) | 1.26 hours | Standard Deviation 3.59 |