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

Rhinitis, Allergic, Perennial Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00449072
• Other study ID #: XRG5029C_3503
• Status: Completed
• Phase: Phase 4
• First received: March 15, 2007
• Last updated: August 7, 2012
• Start date: March 2007
• Est. completion date: October 2011

Study information

• Verified date: October 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 299
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 9 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rhinitis
• Rhinitis, Allergic, Perennial

Intervention

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
• Placebo
Placebo to TAA-AQ was administered intranasally once daily in each nostril during the double-blind period

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
• 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

Locations

Country	Name	City	State
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Growth Velocity	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.	Day 1 to end of treatment (Day 360)	Yes
Secondary	Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS)	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.	For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment)	No
Secondary	Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment	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.	For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment)	No
Secondary	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	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)	Day 120, Day 240 and Day 360	No
Secondary	Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period	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)	Day 120, Day 240 and Day 360	No
Secondary	Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study	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.	Baseline (4-6 months before Day 1), double-blind treatment period (Day 1 to Day 360) and follow-up (Day 361 to Day 420)	No
Secondary	Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study	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.	double-blind treatment period (Day 1 to Day 360)	No
Secondary	24 Hour Urinary Free Cortisol Levels	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].	Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420)	Yes
Secondary	24 Hour Cortisol/Creatinine Ratio	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.	Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420)	Yes
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAE)	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	From Day 1 to 7 days following end of treatment (Day 360)	Yes