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).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 140
- 试验地点
- 8
- 主要终点
- Ratio of Serum Cortisol Area Under Curve [AUC(0-24 hr)] at the End of Treatment to Baseline
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 2 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Placebo nasal spray (Drug)
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.
干预措施: Placebo nasal spray (Drug)
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.
干预措施: Claritin® Syrup (Drug)
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.
干预措施: Claritin® Syrup (Drug)
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.
干预措施: Triamcinolone acetonide aqueous (TAA-AQ) nasal spray (NASACORT AQ) (Drug)
结局指标
主要结局
Ratio of Serum Cortisol Area Under Curve [AUC(0-24 hr)] at the End of Treatment to Baseline
时间窗: 1-3 days prerandomization and 6 weeks postrandomization
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.
次要结局
- Change From Baseline in the Reflective Total Nasal Symptom Score (rTNSS)(From 8-24 days prerandomization up to 6 weeks postrandomization)
- Number of Participants by Relief Level as Evaluated by the Physician(At end of study (43-50 days after randomization))
- Number of Participants by Relief Level as Evaluated by the Participant(At end of study (43-50 days after randomization))
- Number of Participants Using Rescue Medication(From 8 to 24 days prerandomization and randomization to end of study (43-50 days postrandomization))
- The Percent of Days of Rescue Medication Use During the Double-blind Treatment Phase(From randomization to 43-50 days postrandomization)