Hypothalamic-Pituitary-Adrenal (HPA)-Axis Study in Pediatric Subjects With Perennial Allergic Rhinitis (PAR)

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 6-Week Study Designed to Investigate the Effects of BDP Nasal Aerosol on the Hypothalamic-Pituitary-Adrenal (HPA)-Axis in Pediatric Subjects (6 to 11 Years of Age) With Perennial Allergic Rhinitis (PAR)

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Drug: BDP
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BDP Nasal Aerosol 80 mcg/day<br>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. | Drug: BDP<br>* Beclomethasone dipropionate (BDP) 80 mcg/day (40 mcg/spray, 1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.<br>* Other names: Beclomethasone dipropionate;|
| Placebo Comparator: Placebo Nasal Aerosol<br>Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 42 day (6 week) Treatment Period. | Drug: Placebo<br>* Placebo (1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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) | 
| 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. | 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) | 
| 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. | 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) | 
| 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. | 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) | 
| 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. | 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) | 
| 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. | 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) | 
| 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. | Day 1- week 10 | 
| 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 | Screening (Day -21 to -7), End of Study (Day 42) | 
| 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 | Screening (Day -21 to -7), End of Study (Day 42) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric Subjects