Hypothalamic-Pituitary-Adrenal (HPA)-Axis Study in Pediatric Subjects With Perennial Allergic Rhinitis (PAR)
Primary Purpose
Allergic Rhinitis
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
BDP
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Allergic Rhinitis focused on measuring Pediatric Subjects
Eligibility Criteria
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
Sites / Locations
- Teva Investigational Site 10305
- Teva Investigational Site 10304
- Teva Investigational Site 10300
- Teva Investigational Site 10302
- Teva Investigational Site 10301
- Teva Investigational Site 10303
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
BDP Nasal Aerosol 80 mcg/day
Placebo Nasal Aerosol
Arm Description
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.
Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 42 day (6 week) Treatment Period.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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 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.
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.
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.
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.
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
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
Full Information
NCT ID
NCT01697956
First Posted
September 28, 2012
Last Updated
September 10, 2015
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01697956
Brief Title
Hypothalamic-Pituitary-Adrenal (HPA)-Axis Study in Pediatric Subjects With Perennial Allergic Rhinitis (PAR)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Rhinitis
Keywords
Pediatric Subjects
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
99 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BDP Nasal Aerosol 80 mcg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Nasal Aerosol
Arm Type
Placebo Comparator
Arm Description
Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 42 day (6 week) Treatment Period.
Intervention Type
Drug
Intervention Name(s)
BDP
Other Intervention Name(s)
QNASL®, Beclomethasone dipropionate
Intervention Description
Beclomethasone dipropionate (BDP) 80 mcg/day (40 mcg/spray, 1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo (1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.
Primary Outcome Measure Information:
Title
Change From Baseline (Expressed As A Ratio) In 24-Hr Serum Cortisol Weighted Mean Following 6 Weeks Of Treatment
Description
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)
Secondary Outcome Measure Information:
Title
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)
Description
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)
Title
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Description
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)
Title
Maximum Plasma Concentration (Cmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Description
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)
Title
Time to Reach Maximum Plasma Concentration (Tmax) for Beclomethasone-17-monopropionate (17-BMP) and Beclomethasone Dipropionate (BDP)
Description
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)
Title
Terminal Elimination Rate Constant (λz ) for Beclomethasone-17-monopropionate (17-BMP)
Description
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)
Title
Terminal Elimination Half-life (t1/2) for Beclomethasone-17-monopropionate (17-BMP)
Description
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)
Title
Participants With Treatment-Emergent Adverse Events (AEs)
Description
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
Title
Participants With Shifts in Hematology Results From Normal at Screening to High or Low at End of Study
Description
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)
Title
Participants With Shifts in Serum Chemistry Results From Normal at Screening to High or Low at End of Study
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudeesh K Tantry, Ph.D.
Organizational Affiliation
Teva Branded Pharmaceutical Products R&D
Official's Role
Principal Investigator
Facility Information:
Facility Name
Teva Investigational Site 10305
City
Long Beach
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 10304
City
Stockbridge
State/Province
Georgia
Country
United States
Facility Name
Teva Investigational Site 10300
City
Plymouth
State/Province
Minnesota
Country
United States
Facility Name
Teva Investigational Site 10302
City
Normal
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 10301
City
New Braunfels
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 10303
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26250771
Citation
Hampel FC Jr, Nayak NA, Segall N, Small CJ, Li J, Tantry SK. No hypothalamic-pituitary-adrenal function effect with beclomethasone dipropionate nasal aerosol, based on 24-hour serum cortisol in pediatric allergic rhinitis. Ann Allergy Asthma Immunol. 2015 Aug;115(2):137-42. doi: 10.1016/j.anai.2015.05.019.
Results Reference
derived
Learn more about this trial
Hypothalamic-Pituitary-Adrenal (HPA)-Axis Study in Pediatric Subjects With Perennial Allergic Rhinitis (PAR)
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