Clinical trial NCT01154153: Nasacort AQ Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Children With Allergic Rhinitis
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rhinitis, Allergic, Perennial and/or Seasonal
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-06-30
Enrollment: 140
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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 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.

Primary outcomes:
measure: Ratio of Serum Cortisol Area Under Curve [AUC(0-24 hr)] at the End of Treatment to Baseline
timeFrame: 1-3 days prerandomization and 6 weeks postrandomization
Secondary outcomes:
measure: Change From Baseline in the Reflective Total Nasal Symptom Score (rTNSS)
timeFrame: From 8-24 days prerandomization up to 6 weeks postrandomization
measure: Number of Participants by Relief Level as Evaluated by the Physician
timeFrame: At end of study (43-50 days after randomization)
measure: Number of Participants by Relief Level as Evaluated by the Participant
timeFrame: At end of study (43-50 days after randomization)
measure: Number of Participants Using Rescue Medication
timeFrame: From 8 to 24 days prerandomization and randomization to end of study (43-50 days postrandomization)
measure: The Percent of Days of Rescue Medication Use During the Double-blind Treatment Phase
timeFrame: From randomization to 43-50 days postrandomization
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Investigational Site Number 840003
state: California
city: Stockbridge
country: United States
facility: Investigational Site Number 840006
state: Georgia
city: North Dartmouth
country: United States
facility: Investigational Site Number 840007
state: Massachusetts
city: Plymouth
country: United States
facility: Investigational Site Number 840010
state: Minnesota
city: Omaha
country: United States
facility: Investigational Site Number 840001
state: Nebraska
city: Raleigh
country: United States
facility: Investigational Site Number 840008
state: North Carolina
city: Spartanburg
country: United States
facility: Investigational Site Number 840002
state: South Carolina
city: San Antonio
country: United States
facility: Investigational Site Number 840005
state: Texas
Study officials:
affiliation: Sanofi
name: Medical Affairs
role: STUDY_DIRECTOR
References:
citation: Georges G, Kim KT, Ratner P, Segall N, Qiu C. Effect of intranasal triamcinolone acetonide on basal hypothalamic-pituitary-adrenal axis function in children with allergic rhinitis. Allergy Asthma Proc. 2014 Mar-Apr;35(2):163-70. doi: 10.2500/aap.2014.35.3728.