title: HPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitis.
abstract: The effects of intranasal corticosteroids (INSs) on the hypothalamic-pituitary-adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 microg once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2-11 yr with a 1-yr history of PAR (6 months for patients aged 2-3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88-1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 microg QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR.
authors.affiliation: Phelps County Regional Medical Center, 509 E 10th Street, Rolla, MO 65401, USA. itat@fidnet.com
authors.forename: Ita
authors.initials: I
authors.lastname: Tripathy
authors.forename: Arden
authors.initials: A
authors.lastname: Levy
authors.forename: Paul
authors.initials: P
authors.lastname: Ratner
authors.forename: Diane
authors.initials: D
authors.lastname: Clements
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Edward
authors.initials: E
authors.lastname: Philpot
mesh_terms: D000281:Administration, Intranasal; D000730:Androstadienes / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*
chemical_list: D000730:Androstadienes; C523187:fluticasone furoate; D006854:Hydrocortisone