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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT01697956
First received: September 28, 2012
Last updated: September 10, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Allergic Rhinitis
Drug: BDP
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Change From Baseline (Expressed As A Ratio) In 24-Hr Serum Cortisol Weighted Mean Following 6 Weeks Of Treatment [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1- week 10 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Screening (Day -21 to -7), End of Study (Day 42) ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Screening (Day -21 to -7), End of Study (Day 42) ] [ Designated as safety issue: Yes ]

    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



Enrollment: 99
Study Start Date: October 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: BDP
Beclomethasone dipropionate (BDP) 80 mcg/day (40 mcg/spray, 1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.
Other Names:
  • QNASL®
  • Beclomethasone dipropionate
Placebo Comparator: 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.
Drug: Placebo
Placebo (1 spray/nostril, once daily - total 2 sprays/day) as a nasal aerosol.

  Eligibility

Ages Eligible for Study:   6 Years to 11 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01697956

Locations
United States, California
Teva Investigational Site 10305
Long Beach, California, United States
United States, Georgia
Teva Investigational Site 10304
Stockbridge, Georgia, United States
United States, Minnesota
Teva Investigational Site 10300
Plymouth, Minnesota, United States
United States, Pennsylvania
Teva Investigational Site 10302
Normal, Pennsylvania, United States
United States, Texas
Teva Investigational Site 10301
New Braunfels, Texas, United States
Teva Investigational Site 10303
San Antonio, Texas, United States
Sponsors and Collaborators
Teva Pharmaceutical Industries
Investigators
Principal Investigator: Sudeesh K Tantry, Ph.D. Teva Branded Pharmaceutical Products, R&D Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT01697956     History of Changes
Other Study ID Numbers: BDP-AR-307 
Study First Received: September 28, 2012
Results First Received: July 27, 2015
Last Updated: September 10, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Pediatric Subjects

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic
Rhinitis, Allergic, Perennial
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Beclomethasone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 24, 2016