Study of Triamcinolone Acetonide on the Growth Velocity of Children, Ages 3 to 9, With Perennial Allergic Rhinitis (PAR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00449072
First received: March 15, 2007
Last updated: August 7, 2012
Last verified: October 2011
  Purpose

The primary objective of the study was to characterize the difference in prepubescent growth velocity in children 3 to 9 years of age with perennial allergic rhinitis (PAR) treated with triamcinolone acetonide (TAA) nasal spray (NASACORT® AQ 110 μg treatment group) or placebo (NASACORT® AQ placebo group) for 12-months.

The secondary objectives were to compare the following in prepubertal participants treated with TAA nasal spray versus placebo:

  • the 24-hour urinary free cortisol levels and the cortisol/creatinine ratio (to measure the Hypothalamic-Pituitary Adrenal [HPA] axis function)
  • the rate of treatment-emergent-adverse-events (TEAE)
  • global efficacy rated by the investigator and the participant separately
  • the rate of use of rescue medication during the study

Condition Intervention Phase
Rhinitis, Allergic, Perennial
Other: Placebo
Drug: TAA-AQ, Nasacort® AQ
Drug: Claritin®
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel Group Study of the 12 Month Effect of Treatment With Once Daily Triamcinolone Acetonide (NASACORT® AQ Nasal Spray 110 μg) on the Growth Velocity of Children, 3 to 9 Years of Age, With Perennial Allergic Rhinitis (PAR)

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Growth Velocity [ Time Frame: Day 1 to end of treatment (Day 360) ] [ Designated as safety issue: Yes ]

    Individual participant's growth velocity over double-blind treatment period was calculated using a linear regression of height over time.

    Height was measured on the same wall-mounted Harpenden stadiometer with the participant barefoot and in light clothing.



Secondary Outcome Measures:
  • Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS) [ Time Frame: For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment) ] [ Designated as safety issue: No ]

    PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale:

    • 0 = symptom absent
    • 1 = mild (present but not annoying to self)
    • 2 = moderate (annoying to self but not interfering with sleep or daily living)
    • 3 = severe (interfered with daily living and/or sleep)

    TNSS was the sum of the individual symptom scores (ranging 0-3), and TNSS ranged from 0 (best outcome) to 12 (worst outcome). A negative value for change represents an improvement in symptoms.


  • Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment [ Time Frame: For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment) ] [ Designated as safety issue: No ]

    PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale:

    • 0 = symptom absent
    • 1 = mild (present but not annoying to self)
    • 2 = moderate (annoying to self but not interfering with sleep or daily living)
    • 3 = severe (interfered with daily living and/or sleep)

    Individual symptom scores ranged from 0 (best outcome) to 3 (worst outcome). A negative value for change represents an improvement in symptoms.


  • Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period [ Time Frame: Day 120, Day 240 and Day 360 ] [ Designated as safety issue: No ]

    Global efficacy was assessed by the participant (with the help of a parent/guardian/caregiver) using the following scale:

    • 0 = no relief (symptoms unchanged or worse than before)
    • 1 = slight relief (symptoms were present and only minimally improved)
    • 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved)
    • 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome)
    • 4 = complete relief (virtually no symptom present)

  • Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period [ Time Frame: Day 120, Day 240 and Day 360 ] [ Designated as safety issue: No ]

    Global efficacy was assessed by the investigator using the following scale:

    • 0 = no relief (symptoms unchanged or worse than before)
    • 1 = slight relief (symptoms were present and only minimally improved)
    • 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved)
    • 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome)
    • 4 = complete relief (virtually no symptom present)

  • Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study [ Time Frame: Baseline (4-6 months before Day 1), double-blind treatment period (Day 1 to Day 360) and follow-up (Day 361 to Day 420) ] [ Designated as safety issue: No ]

    Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary.

    The percentage of participants who used the rescue medication during each of the study periods is reported.


  • Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study [ Time Frame: double-blind treatment period (Day 1 to Day 360) ] [ Designated as safety issue: No ]

    Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary.

    The percentage of days that participants used the rescue medication during the double-blind treatment phase of the study.


  • 24 Hour Urinary Free Cortisol Levels [ Time Frame: Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420) ] [ Designated as safety issue: Yes ]
    Urine cortisol levels was determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be [1.4 - 21 μg/24 hours].

  • 24 Hour Cortisol/Creatinine Ratio [ Time Frame: Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420) ] [ Designated as safety issue: Yes ]
    Urine cortisol and creatinine levels were determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be [1.4 - 21 μg/24 hours]. No normal range is available for cortisol/creatinine ratio.

  • Number of Participants With Treatment-emergent Adverse Events (TEAE) [ Time Frame: From Day 1 to 7 days following end of treatment (Day 360) ] [ Designated as safety issue: Yes ]

    Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind investigational product (IP) are defined as TEAEs.

    A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose:

    • Resulted in death
    • Was life-threatening
    • Required inpatient hospitalization or prolongation of existing hospitalization
    • Resulted in persistent or significant disability/incapacity
    • Was a congenital anomaly/birth defect
    • Was a medically important event


Enrollment: 299
Study Start Date: March 2007
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

3 to 9 year old participants with Perennial Allergic Rhinitis (PAR) administered

  • Placebo in the baseline/screening period to demonstrate administration of investigational product (IP) with the nasal spray bottle
  • Placebo in the double-blind treatment period

All participants were provided Children's Claritin® Syrup as a rescue medication.

Other: Placebo
Placebo to TAA-AQ was administered once at the study site in each nostril during the baseline/screening period to demonstrate intranasal IP administration
Other: Placebo
Placebo to TAA-AQ was administered intranasally once daily in each nostril during the double-blind period
Drug: Claritin®
Participants were provided Children's Claritin® Syrup (5 mg of loratadine per 5 mL), as rescue medication for the relief of allergic rhinitis (AR) symptoms, and could be used throughout the study on an as needed basis according to the Food and Drug Administration-approved manufacturer's label
Active Comparator: TAA-AQ

3 to 9 year old participants with Perennial Allergic Rhinitis (PAR) administered

  • Placebo in the baseline/screening period to demonstrate administration of IP with the nasal spray bottle
  • Triamcinolone acetonide (TAA-AQ) in the double-blind treatment period

All participants were provided Children's Claritin® Syrup as a rescue medication.

Other: Placebo
Placebo to TAA-AQ was administered once at the study site in each nostril during the baseline/screening period to demonstrate intranasal IP administration
Drug: TAA-AQ, Nasacort® AQ
110 μg TAA-AQ was administered once daily intranasally (1 spray delivering 55 μg of TAA-AQ in each nostril) during the double-blind treatment period
Drug: Claritin®
Participants were provided Children's Claritin® Syrup (5 mg of loratadine per 5 mL), as rescue medication for the relief of allergic rhinitis (AR) symptoms, and could be used throughout the study on an as needed basis according to the Food and Drug Administration-approved manufacturer's label

Detailed Description:

The study consisted of:

  • a 4- to 6-month screening/baseline period
  • a 12-month (up to Day 360+/-5 days) double-blind treatment period starting on Day 1
  • a 2-month follow-up period (up to Day 420+/-5 days)
  Eligibility

Ages Eligible for Study:   3 Years to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Participants meeting the following eligibility criteria were enrolled.

Inclusion criteria:

  1. Male participants [3 years to <= 9 years + 0 days old] at Visit 1 and no older than [9 years + 120 days] at Visit 3; and, female participants [3 years to <= 8 years + 0 days old] at Visit 1 and no older than [8 years + 120 days] at Visit 3: all sexually prepubertal (ie, Stage 1 of Tanner Classification of sexual maturity) at Visit 1 and Visit 3. A 5-day extension to the age upper bound was permitted under certain circumstances to enable scheduling of Visits 1 and 3
  2. At least a one year history of PAR as assessed and documented by the investigator (with or without seasonal allergic rhinitis [SAR])
  3. Positive skin test (prick or intradermal) to a perennial allergen that was present in the participant's environment. A skin test was considered positive if the wheal produced by the allergen was equal to or greater than that caused by positive control (histamine) or was at least 3 mm (prick test) or 7 mm (intradermal test) greater than the wheal of negative control (saline). If a skin test could not be performed, the radioallergosorbent test (RAST) would be used as an alternative. Documented historical skin testing or RAST performed during the past year were acceptable
  4. Height within the 3rd and 97th percentiles at screening (Visit 1), Visit 2, and at randomization (Visit 3)
  5. Symptomatic (daily AM instantaneous total nasal symptom score was >= 4 out of 12) on any 4 out of the last 7 consecutive days immediately prior to and including the morning of Visit 3. Symptom ratings were to be completed with the help of a parent/guardian/caregiver
  6. Written informed consent and ability of parent or legal guardian of the participant to give a written informed consent before any study related procedures. Participants 7 years of age and older must have provided a signed assent form
  7. Participants had to be toilet-trained

Exclusion criteria:

  1. Gross nasal anatomical deformities including large polyposis and marked deviated septum
  2. History of or current cataract or glaucoma
  3. History of hypersensitivity to the corticosteroids or to any excipient of the investigational product
  4. Participant was the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
  5. Height, weight, or body mass index (BMI)-for-age below the 3rd or above the 97th percentile at Visits 1, 2, or 3
  6. Treatment with systemic corticosteroids (oral, intravenous, intramuscular, or intra-articular) within 3 months prior to Visit 1
  7. Treatment with systemic corticosteroids for >2 courses received up to 1 year before Visit 1 was exclusionary. Up to 2 courses of systemic corticosteroids each course not exceeding 14 days up to 1 year before Visit 1 was allowed.
  8. Treatment with inhaled, intranasal, or high potency topical corticosteroid exposure within 6 weeks prior to Visit 1. Mild asthma that was well-controlled and without the use of inhaled corticosteroids within 6 weeks before screening (Visit 1).
  9. Immunotherapy, except stable (>=1 month) maintenance schedule before Visit 1.
  10. Treatment with any substance before Visit 1 that might have affected growth velocity and/or linear growth, such as, but not be limited to methylphenidate hydrochloride, thyroid hormone, growth hormone, anabolic steroids, calcitonin, estrogens, progestins, bisphosphonates, anticonvulsants, or phosphate-binding antacids
  11. Treatment with any investigational product or device in the 30 days before Visit 1 or at any time throughout the duration of this trial (Visit 1 through Visit 11).
  12. Bone age as assessed by X-ray of the left hand and wrist that was outside +/- 1.5 years of participants chronological age at Visit 2. Right hand and wrist were to be radiographed in the event of bone injury to the left hand or wrist.
  13. Unresolved upper respiratory tract infection, sinus infection or nasal candidiasis (i.e., symptomatic or under treatment) within the last 2 weeks before Visit 3.
  14. Participants or parent/guardian/caregiver unable to demonstrate correct administration of the investigational product at Visit 1.
  15. Concomitant disease other than PAR which could have interfered with the study procedures or outcomes as determined by the investigator.
  16. History of hospitalization due to asthma within 1 year before screening (Visit 1).
  17. Abnormal 24-hour urinary free cortisol level assessed at screening (Visit 2).

The above information was not intended to contain all considerations relevant to potential participation in a clinical trial.

  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: NCT00449072

Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Akbar Akbary, MD Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00449072     History of Changes
Other Study ID Numbers: XRG5029C_3503
Study First Received: March 15, 2007
Results First Received: June 29, 2012
Last Updated: August 7, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic, Perennial
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Nose Diseases
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Respiratory Tract Diseases
Respiratory Tract Infections
Loratadine
Triamcinolone
Triamcinolone Acetonide
Triamcinolone diacetate
Triamcinolone hexacetonide
Anti-Allergic Agents
Anti-Inflammatory Agents
Antipruritics
Dermatologic Agents
Enzyme Inhibitors
Glucocorticoids
Histamine Agents
Histamine Antagonists
Histamine H1 Antagonists
Histamine H1 Antagonists, Non-Sedating
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 29, 2014