A randomized, double-blind, placebo-controlled, parallel-group study of once-daily inhaled fluticasone furoate on the hypothalamic-pituitary-adrenocortical axis of children with asthma

Abstract

Background: 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.

Methods: This 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.

Results: Fifty-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.

Conclusions: Six 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 registration: This study is registered in ClinicalTrials.gov (NCT02483975). Date of submission: 25 June 2015.

Keywords: Asthma; Fluticasone furoate (FF); Pediatric; Safety, HPA axis; Serum cortisol.

Fig. 1

Study design. Subjects received open-label montelukast during the run-in and treatment periods, and albuterol/salbutamol as needed to treat acute asthma symptoms. *Days 5–7 after the end of treatment. FF 50 QD fluticasone furoate 50 µg once daily

Fig. 2

a Adjusted treatment ratios for SC weighted mean (0–24 h) at week 6; b geometric mean (95% CI) SC concentration–time profile by treatment group and visit (SC population). CI confidence interval, FF 50 QD fluticasone furoate 50 µg once daily, h hours, SC serum cortisol