Abstract
BackgroundTo evaluate the effects of fluticasone furoate on the hypothalamic–pituitary–adrenocortical axis, and the safety and tolerability of fluticasone furoate treatment in children with asthma.MethodsThis was a randomized, double-blind, placebo-controlled, multicenter, stratified, parallel-group, non-inferiority study of fluticasone furoate 50 µg inhalation powder administered once daily. The study enrolled children (aged 5–11 years inclusive) with a documented diagnosis of asthma for ≥ 6 months and a Childhood Asthma Control Test score of > 19. After a 7–14-day run-in period, eligible subjects were stratified by age and randomized to fluticasone furoate 50 µg once daily or placebo once daily via ELLIPTA for 6 weeks. The primary endpoint was the change from baseline (expressed as a ratio) in 0–24-h weighted mean serum cortisol at the end of the treatment period.ResultsFifty-six randomized subjects received fluticasone furoate 50 µg once daily and 55 received placebo. The primary analysis was performed in the serum cortisol population (n = 104) and demonstrated that fluticasone furoate 50 µg once daily was non-inferior to placebo (ratio = 0.93; 95% confidence interval 0.8096, 1.0620), as the lower limit of the 95% confidence interval for the geometric mean treatment ratio of fluticasone furoate 50 µg once daily versus placebo was greater than 0.80. Findings from the intent-to-treat population (n = 111) were similar.ConclusionsSix weeks of treatment with inhaled fluticasone furoate 50 µg once daily had no clinically relevant effect on the hypothalamic–pituitary–adrenocortical axis function of children, as measured by 24-h serum cortisol profiles. The primary analysis showed that fluticasone furoate 50 µg once daily was non-inferior to placebo. Fluticasone furoate 50 µg once daily was well tolerated and no new safety concerns emerged during the study.Trial registrationThis study is registered in ClinicalTrials.gov (NCT02483975). Date of submission: 25 June 2015.
Highlights
To evaluate the effects of fluticasone furoate on the hypothalamic–pituitary–adrenocortical axis, and the safety and tolerability of fluticasone furoate treatment in children with asthma
107 (96%) subjects completed the study (Additional file 2: Figure S1), 104 (94%) subjects were included in the serum cortisol (SC) population, 108 (97%) subjects were included in the urinary cortisol (UC) population and 106 (95%) were included in the PK population
While Inhaled corticosteroids (ICS) are established as an effective antiinflammatory treatment for all severities of persistent asthma [1], their use is associated with a dose-related risk of HPA axis suppression [10, 11]
Summary
To evaluate the effects of fluticasone furoate on the hypothalamic–pituitary–adrenocortical axis, and the safety and tolerability of fluticasone furoate treatment in children with asthma. Inhaled corticosteroids (ICS) are a mainstay of treatment in adults and children with persistent asthma of varying severity [1]. ICS are effective anti-inflammatory treatments of persistent asthma [1], their excessive or long-term use at high dosages is associated with hypothalamic–pituitary–adrenocortical (HPA) axis suppression in adults and children, potentially leading to adrenal insufficiency and in severe cases, adrenal crisis and death [2,3,4]. The safety of inhaled FF in combination with the longacting β2-agonist vilanterol (VI) on the HPA axis in adult and adolescent (12–17 years of age) patients with asthma has been established [6]. Doubleblind, crossover studies of FF 100 μg or FF/VI 100/25 μg found no evidence of serum cortisol (SC) suppression in children (aged 5–11 years) with persistent asthma, suggesting this FF dose does not affect the HPA axis in this patient population [8, 9]
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