Safety and Tolerability of Fluticasone Furoate Nasal Spray Once Daily in Paediatric Patients Aged 6–11 Years with Allergic Rhinitis: Subanalysis of Three Randomized, Double-Blind, Placebo-Controlled, Multicentre Studies

• Published in: Clinical drug investigation 2009-01, Vol.29 (2), p.79-86
• Main Authors: Meltzer, Eli O., Tripathy, Ita, Máspero, Jorge F., Wu, Wei, Philpot, Ed
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - adverse effects; Adrenal Cortex Hormones - therapeutic use; Aerosols; Androstadienes - administration & dosage; Androstadienes - adverse effects; Androstadienes - therapeutic use; Anti-Allergic Agents - administration & dosage; Anti-Allergic Agents - adverse effects; Anti-Allergic Agents - therapeutic use; Child; Female; Humans; Hydrocortisone - blood; Hydrocortisone - urine; Internal Medicine; Male; Medicine; Medicine & Public Health; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial - drug therapy; Rhinitis, Allergic, Seasonal - drug therapy
• ISSN: 1173-2563; 1179-1918
• DOI: 10.2165/0044011-200929020-00002

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 ≥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 εg (n = 297; 2-week SAR and 12-week PAR studies only), FFNS 110 εg (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 εg, FFNS 110 εg and placebo groups, respectively. The most common AEs were headache (8%, 9% and 8% in the FFNS 55 εg, FFNS 110 εg 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. Ophth