Nasacort AQ Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Children With Allergic Rhinitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01154153
First received: June 22, 2010
Last updated: June 21, 2012
Last verified: June 2012
  Purpose

The primary objective was to evaluate the effect of a 6-week treatment with TAA-AQ (110 μg) and TAA-AQ (220 μg) once daily (QD) versus placebo on hypothalamic-pituitary-adrenal (HPA) axis function as measured by serum cortisol AUC(0-24 hr) in children (>=2 to <12 years old) with allergic rhinitis (AR).


Condition Intervention Phase
Rhinitis, Allergic, Perennial and/or Seasonal
Drug: Placebo nasal spray
Drug: Triamcinolone acetonide aqueous (TAA-AQ) nasal spray (NASACORT AQ)
Drug: Claritin® Syrup
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Pharmacodynamic Effect of a 6-week Treatment With Triamcinolone Acetonide Aqueous Nasal Spray 110 μg and 220 μg Once Daily on Basal Hypothalamic-Pituitary-Adrenal (HPA) Axis Function in Children [>=2 to < 12 Years of Age] With Allergic Rhinitis (AR).

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Ratio of Serum Cortisol Area Under Curve [AUC(0-24 hr)] at the End of Treatment to Baseline [ Time Frame: 1-3 days prerandomization and 6 weeks postrandomization ] [ Designated as safety issue: No ]

    Blood samples were collected over a 24-hour period (at 0, 2, 4, 8, 12, 20, and 24 hours), with 0 hour being between 8:00AM to 9:00AM, immediately prior to investigational product (IP) administration. AUC (0-24hr) was calculated using the trapezoid rule, and was normalized by dividing the AUC(0-24 hr) by the actual sample collection interval between 0-hour and 24-hour blood draw times.

    Ratio in Serum Cortisol AUC(0-24 hr) = (Serum Cortisol AUC[0-24 hr] at 6 weeks postrandomization)/(Serum Cortisol AUC[0-24 hr] at 1-3 days prerandomization). Log transformation was used for the analysis.



Secondary Outcome Measures:
  • Change From Baseline in the Reflective Total Nasal Symptom Score (rTNSS) [ Time Frame: From 8-24 days prerandomization up to 6 weeks postrandomization ] [ Designated as safety issue: No ]

    Every morning, participants rated the severity of symptoms experienced over the previous 24 hours using scale from 0-3, where 0=symptoms absent, 1=mild, 2=moderate, and 3=severe symptoms (interfere with daily living or sleep) for each symptom (nasal congestion, nasal itching, sneezing, and runny nose). The rTNSS was the sum of the individual symptom scores, ranged from 0-12 (where 12 reflected the worst symptoms).

    Change from baseline in the rTNSS = mean rTNSS (double-blind treatment phase) - mean rTNSS (screening phase).


  • Number of Participants by Relief Level as Evaluated by the Physician [ Time Frame: At end of study (43-50 days after randomization) ] [ Designated as safety issue: No ]
    Efficacy of treatment was assessed by the physician using a scale from 0-4 for relief levels, where 0 = no relief (symptoms unchanged or worsened than before), 1 = slight relief (symptoms present and only minimally improved), 2 = moderate relief (symptoms are present and may be troublesome, but are noticeably improved), 3 = marked relief (symptoms are greatly improved and although present are scarcely troublesome) and 4 = complete relief (virtually no symptom present).

  • Number of Participants by Relief Level as Evaluated by the Participant [ Time Frame: At end of study (43-50 days after randomization) ] [ Designated as safety issue: No ]
    Efficacy of treatment was assessed by the participant using a scale from 0-4 for relief levels, where 0 = no relief (symptoms unchanged or worsened than before), 1 = slight relief (symptoms present and only minimally improved), 2 = moderate relief (symptoms are present and may be troublesome, but are noticeably improved), 3 = marked relief (symptoms are greatly improved and although present are scarcely troublesome) and 4 = complete relief (virtually no symptom present).

  • Number of Participants Using Rescue Medication [ Time Frame: From 8 to 24 days prerandomization and randomization to end of study (43-50 days postrandomization) ] [ Designated as safety issue: No ]
    The number of participants using the rescue medication (Claritin®) during the single-blind screening phase (the time from 8-24 days before randomization up to the day before randomization) and during the double-blind treatment phase (the time from randomization to end of study).

  • The Percent of Days of Rescue Medication Use During the Double-blind Treatment Phase [ Time Frame: From randomization to 43-50 days postrandomization ] [ Designated as safety issue: No ]
    The percent of days of rescue medication used during the double-blind treatment phase was calculated. For participants who did not use any rescue medication, the percentage of days using rescue medication was set to be 0.


Enrollment: 140
Study Start Date: June 2010
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
  • placebo during the screening phase and
  • placebo during the treatment phase.

All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.

Drug: Placebo nasal spray
1 spray/nostril, once daily in the morning, for 8 to 24 days during the screening phase.
Drug: Placebo nasal spray

Treatment assignment was randomized with stratification by sex and age group (>=2 to <6, >=6 to <12 years old).

  • For children who were >=2 to <6 years old, 1 spray/nostril, once daily in the morning, for 6 weeks, during the double-blind treatment phase.
  • For children who were >= 6 yrs to <12 years old, either 1 spray/nostril or 2 sprays/nostril, once daily in the morning, for 6 weeks, during the double-blind treatment phase.
Drug: Claritin® Syrup
Children's Claritin® Syrup [5 mg of loratadine per 5 mL] could be taken orally for the relief of AR symptoms throughout the study on an as needed basis, according to the Food and Drug Administration-approved manufacturer's label.
Experimental: TAA-AQ
  • placebo during the screening phase and
  • TAA-AQ (Nasacort AQ) during the treatment phase.

All children had the option to take rescue medication, (Claritin®) as needed to relieve symptoms of AR.

Drug: Placebo nasal spray
1 spray/nostril, once daily in the morning, for 8 to 24 days during the screening phase.
Drug: Triamcinolone acetonide aqueous (TAA-AQ) nasal spray (NASACORT AQ)

Treatment assignment was randomized with stratification by sex and age group (>=2 to <6, >=6 to <12 years old).

  • For children who were >=2 to <6 years old, 1 spray/nostril (110 µg TAA-AQ), once daily in the morning, for 6 weeks, during the double-blind treatment phase.
  • For children who were >=6 yrs to <12 years old, either 1 spray/nostril (110 µg TAA-AQ) or 2 sprays/nostril (220 µg TAA-AQ), once daily in the morning, for 6 weeks, during the double-blind treatment phase.
Drug: Claritin® Syrup
Children's Claritin® Syrup [5 mg of loratadine per 5 mL] could be taken orally for the relief of AR symptoms 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 run-in single-blind screening phase (prerandomization) followed by an approximately 6-week double-blind treatment phase (postrandomization).

Total study duration per participant lasted from 7.5 to 13 weeks and consisted of:

  • Screening and single-blind phases (these 2 phases ran concurrently, prerandomization) for 8 to 24 days. During the screening phase participants were given a single-blind placebo nasal spray to enable them to practice their intranasal application technique once daily in the morning (1 actuation/nostril).
  • Randomization to the double-blind treatment phase. Treatment assignment was randomized with stratification by sex and age group (>=2 to <6, >=6 to <12 years old).
  • Double-blind treatment phase which lasted at least 42 days and ran up to 47 days. Participants were administered either TAA-AQ nasal spray or placebo nasal spray.
  • An evaluation at the end of treatment 1-3 days after completion of the double-blind phase.
  Eligibility

Ages Eligible for Study:   2 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Participants who met the following criteria were eligible for this study:

Inclusion Criteria:

  • History of AR documented by the investigator, as follows:

    • At least a 1-year clinical history (6-month history if the participant was >= 2 to < 4 years of age) of perennial allergic rhinitis (PAR); or a clinical history of seasonal allergic rhinitis (SAR) over 2 seasons and
    • positive skin test (prick or intradermal) to a seasonal or perennial allergen that was present in the participant's environment at time of screening.
  • Written informed consent and ability of parent/legal guardian of the participant to give a written informed consent before any study related procedures. Participants >=7 years of age (or younger according to the governing institutional review board [IRB]) had to provide a signed assent form

Exclusion Criteria:

  • Concomitant medical condition that might have interfered with the administration of a nasal spray, including anatomical abnormalities of the nose, face (eg, polyposis, markedly deviated septum)
  • Presence of any active, untreated, or clinically significant musculoskeletal, endocrinologic, gastrointestinal, hepatic, respiratory, cardiovascular, or neurological condition that might have interfered with the study
  • Any conditions or treatment that might have affected the HPA axis or the plasma cortisol assay, including but not limited to:

    • Documented disorder involving the hypothalamus, pituitary, or adrenal gland
    • Current use of serotonergic, dopaminergic, adrenergic, cholinergic agonists and antagonists, opiates, immunomodulatory, hormonal drugs, and lipid-lowering agents
    • Treatment with systemic corticosteroids (oral, intravenous, intramuscular, or intra-articular) within 3 months prior to Visit 1
    • 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
    • Treatment with inhaled, intranasal, or high-potency topical corticosteroids within 6 weeks of Visit 1
    • History of hospitalization due to asthma within 1 year before screening. Participants with mild asthma that was well-controlled without the use of inhaled corticosteroids within 6 weeks prior to Visit 1 were eligible for the study
  • Any clinically significant (as determined by the investigator) abnormal laboratory test at Visit 1
  • Morning serum cortisol outside the reference range at Visit 1
  • Any of the following missing serum cortisol samples from the Visit-2 collection: first sample (before administration of investigational product), 20-hour sample, 24-hour sample, or any 2 consecutive samples
  • Any medical condition where use of corticosteroids might have been contraindicated or could have led to disease exacerbation (eg, glaucoma, cataract, ocular herpes simplex, tuberculosis, growth retardation)
  • History of hypersensitivity to corticosteroids or to the rescue medication, investigational product, or to any of their excipients
  • Unresolved upper respiratory tract infection, sinus infection, or nasal candidiasis (ie, symptomatic or under treatment) within the last 2 weeks prior to Visit 1 and Visit 3
  • Females of childbearing potential not protected by effective contraceptive method of birth control or were unwilling to abstain from sexual activity and/or, were unwilling or unable to test for pregnancy. Only female adolescent with onset of menses were to be checked by serum pregnancy test at Visit 1
  • Pregnant female adolescent (who tested positive for pregnancy at Visit 1) 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: NCT01154153

Locations
United States, California
Investigational Site Number 840003
Cypress, California, United States, 90630
United States, Georgia
Investigational Site Number 840006
Stockbridge, Georgia, United States, 30281
United States, Massachusetts
Investigational Site Number 840007
North Dartmouth, Massachusetts, United States, 02747
United States, Minnesota
Investigational Site Number 840010
Plymouth, Minnesota, United States, 55441
United States, Nebraska
Investigational Site Number 840001
Omaha, Nebraska, United States, 68144
United States, North Carolina
Investigational Site Number 840008
Raleigh, North Carolina, United States, 27607
United States, South Carolina
Investigational Site Number 840002
Spartanburg, South Carolina, United States, 29307
United States, Texas
Investigational Site Number 840005
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Medical Affairs Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01154153     History of Changes
Other Study ID Numbers: TRICA_L_04286
Study First Received: June 22, 2010
Results First Received: September 21, 2011
Last Updated: June 21, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 24, 2014