Background: Fluticasone furoate (FF) is an inhaled corticosteroid that is structurally and functionally distinct from fluticasone propionate and is under development as a once-daily therapy for asthma. Objective: The objective of this study was to estimate the treatment differences (with 95% Cl) in efficacy and safety profile between FF administered once daily in the morning and evening via Rotadisk Diskhaler (see text) in patients with persistent asthma. No hypothesis testing was performed for this comparison. Methods: This was a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. Patients (ages 16-55 years; peak expiratory flow [PEF] 50%-90% predicted) were randomized to receive 1 of 3 doses of FF Rotadisk or placebo daily for 4 weeks. The sponsor, GlaxoSmithKline, designed the study and selected the study sites. The primary end point was change from baseline in daily trough (pretreatment, prebronchodilator) PEF during the treatment period with FF Rotadisk 100 mu g once daily in the morning compared with 100 mu g once daily in the evening. Other end points included change from baseline in forced expiratory volume in 1 second, asthma symptom score, adverse events (AEs), 24-hour urinary cortisol excretion, and FF pharmacokinetics. Results: Five hundred and seventy-five patients (mean age 36.6 years, 56.9% female) formed the intent-to-treat population and were randomly allocated to FF Rotadisk 100 mu g once daily in the morning (n = 144), FF Rotadisk 100 mu g once daily in the evening (n = 146), FF Rotadisk 250 mu z once daily in the evening (n = 142), or placebo (n = 143). Of these patients, 526 (91.5%) completed the study. A smaller proportion of patients in the placebo group (86.7%) than in the active treatment groups completed the study. Mean difference in PEF change from baseline with FF Rotadisk 100 mu g once daily in the morning relative to evening was +13.4 L/min (95% Cl, 2.3-24.4). However, morning trough values might have been affected by higher placebo response after morning dosing (18.8 vs 8.8 L/min). Trough PEF improved relative to placebo (P <= 0.005), with little difference between FF Rotadisk 100 mu g morning (19 L/min) and evening (16 L/min) dosing, as with other efficacy measures. Frequencies of all-cause AEs were similar with FF Rotadisk (32%-39%, 2 serious AEs) and placebo (37%, 1 serious AE). No serious AEs were deemed by the investigator to be related to study treatment. Twenty-four-hour urinary cortisol increased from baseline in all groups, but the increase was significantly lower with FF Rotadisk 250 mu g group than placebo. Conclusion: FF Rotadisk administered once daily in the morning or evening was well tolerated and associated with improvements in lung function and asthma symptoms compared with placebo. Improvements seen for FF Rotadisk 100 mu g appear to be comparable for morning and evening dosing. Clinical.trials.gov NCT01499446. (Clin Ther. 2012;34:1683-1695) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.
