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

Sanofi

Status and phase: Completed; Phase 4

Conditions: Rhinitis, Allergic, Perennial and/or Seasonal

Treatments: Drug: Triamcinolone acetonide aqueous (TAA-AQ) nasal spray (NASACORT AQ); Drug: Placebo nasal spray; Drug: Claritin® Syrup

Study type: Interventional

Funder types: Industry

Identifiers

NCT01154153

TRICA_L_04286

Details and patient eligibility

About

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).

Full 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.

Enrollment: 140 patients

Sex: All

Ages: 2 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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140 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

* 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.

Treatment:

Drug: Claritin® Syrup

Drug: Placebo nasal spray

Drug: Placebo nasal spray

TAA-AQ

Experimental group

Description:

* 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.

Treatment:

Drug: Triamcinolone acetonide aqueous (TAA-AQ) nasal spray (NASACORT AQ)

Drug: Claritin® Syrup

Drug: Placebo nasal spray

Drug: Placebo nasal spray