Background: Fluticasone furoate is a novel enhanced-affinity corticosteroid that has demonstrated favourable safety and tolerability in paediatric patients. Three pivotal phase III studies were conducted in children as young as 2 years of age; however, because the European Medicines Agency has recently approved fluticasone furoate for use in children aged>or=6 years, a subanalysis has been conducted to support safety and tolerability in the 6- to 11-year age group.
Methods: All three trials included in the subanalysis were randomized, double-blind, placebo-controlled, parallel-group studies: a 2-week US study in patients with seasonal allergic rhinitis (SAR), a 12-week global study in patients with perennial allergic rhinitis (PAR) and a 6-week US hypothalamic-pituitary-adrenal (HPA) axis safety study in patients with PAR. Randomized patients received once-daily treatment with either fluticasone furoate nasal spray (FFNS) 55 microg (n=297; 2-week SAR and 12-week PAR studies only), FFNS 110 microg (n=321) or vehicle placebo nasal spray (n=330). Safety assessments included clinical adverse event (AE) monitoring, clinical laboratory tests, detailed nasal examinations, monitoring of vital signs, and 12-lead ECGs. Ophthalmic examinations (12-week PAR study only) were conducted by an ophthalmologist or optometrist before randomization and at final treatment visit. Twenty-four-hour urinary cortisol (UC) excretions (6- and 12-week PAR studies) and serum cortisol (SC) concentrations (6-week PAR study only) were assessed at specified timepoints over 24 hours as a measure of HPA axis function. In the 6-week HPA axis safety study in patients with PAR, 24-hour UC and SC samples were collected in a domiciled (clinical) setting.
Results: No unexpected safety results were observed in patients aged 6-11 years enrolled in the three studies. Across all three trials, AEs considered by the investigator to be drug related were observed in 10%, 7% and 8% of patients in the FFNS 55 microg, FFNS 110 microg and placebo groups, respectively. The most common AEs were headache (8%, 9% and 8% in the FFNS 55 microg, FFNS 110 microg and placebo groups, respectively), nasopharyngitis (5%, 6% and 5%, respectively), pharyngolaryngeal pain (5%, 3% and 4%, respectively), epistaxis (4% in both active treatment groups and 4% in the placebo group) and pyrexia (3% in both active treatment groups and 2% in the placebo group). Findings from nasal examinations were similar across the treatment and placebo groups. Ophthalmic examinations found no differences between the treatment groups for mean change from baseline in intraocular pressure (assessed in the 12-week PAR study only), and no posterior subcapsular cataracts were reported in patients in either FFNS-treatment group. In the 6-week HPA axis study, 24-hour SC geometric mean concentrations were similar for FFNS and placebo groups. The lower limit of two-sided 95% confidence interval (CI) for the treatment ratio was greater than the prespecified noninferiority margin of 0.8 (treatment ratio=0.92, 95% CI 0.80, 1.05).
Conclusions: FFNS has a favourable safety and tolerability profile in patients aged 6-11 years with PAR or SAR.