Objectives: Fluticasone furoate (FF; inhaled corticosteroid) combined with vilanterol (VI; long-acting beta(2) agonist) is a once-daily therapy for asthma and chronic obstructive pulmonary disease. This 12-week phase III study compared the efficacy and safety of once-daily (evening dosing) FF/VI100/25mcg versus FF 100mcg (primary objective) and FF/VI100/25mcg versus FF/VI200/25mcg (descriptive comparison only) in patients (n=1039) 12 years with moderate-to-severe persistent asthma. Methods: The primary end point was weighted mean (wm) 0-24-h serial forced expiratory volume in 1s (FEV1) at week 12. Secondary end points (change from baseline) were trough FEV1 and the proportion (%) of rescue-free 24-h periods (both powered), the proportion (%) of symptom-free 24-h periods, and morning and evening peak expiratory flow (PEF). Safety data (adverse events, AEs) were collected throughout. Results: Compared with FF 100mcg, FF/VI100/25mcg significantly improved wmFEV(1) (p<0.001), trough FEV1 (p=0.014), % rescue-free (p<0.001), % symptom-free (p=0.002) 24-h periods, and morning and evening PEF (p<0.001). FF/VI 200/25mcg produced small numerical improvements versus FF/VI 100/25mcg for all end points. Incidence of AEs was similar across groups. Conclusions: FF/VI 100/25mcg resulted in significant improvements in all primary and secondary end points versus FF 100mcg. Numerical improvements occurred with FF/VI 200/25mcg versus FF/VI 100/25mcg. All treatments were well tolerated.

The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β₂ agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV₁) weighted mean (wm) 0-24 h serial FEV1. Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG. FF/VI significantly improved trough FEV1 and wmFEV₁ versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.

Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing. The study described here was a double-blind, double-dummy, randomised, placebo-controlled trial, the aim of which was to assess the efficacy of once-daily VI compared with placebo in patients with persistent asthma. The primary endpoint was change from baseline in 24-hour weighted mean forced expiratory volume in 1 second after 12 weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS.

ABSTRACT Background: Fluticasone furoate (FF) is a novel enhanced-affinity corticosteroid for the treatment of allergic rhinitis, delivered by a unique side-actuated device. This study was designed to investigate the efficacy and safety of FF nasal spray (FFNS) 110 μg once daily compared with placebo in adults and adolescents (aged ≥12 years) with seasonal allergic rhinitis (SAR) symptoms caused by mountain cedar (Juniperus ashei) pollen. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, phase III study conducted over a 2-week period (between 10 December 2004 and 19 January 2005) at seven study sites, in Austin, Texas, USA, and San Antonio, Texas, two metropolitan cities in the central Texas Hill Country located approximately 80 miles apart. Adult and adolescent patients (aged ≥12 years) with SAR, who were sensitized to mountain cedar (Juniperus ashei) pollen, were randomized to receive either FFNS 110 μg (n = 152) or placebo (n = 150) once daily. Patients rated the severity of each nasal symptom (rhinorrhea, nasal congestion, nasal itching, and sneezing) and ocular symptom (redness, watery eyes, itching and burning) on a 4-point categorical scale (0 = none, 3 = severe) in a reflective and instantaneous manner. Patients also rated their overall evaluation of response to therapy. Results: FFNS significantly improved the nasal symptoms of SAR compared with placebo. The least square (LS) mean difference in the reflective total nasal symptom score (TNSS) was −0.777 (p = 0.003). A significant reduction in morning pre-dose instantaneous TNSS was also observed compared with placebo (LS mean difference −0.902; p < 0.001). Patients receiving FFNS had significantly greater improvements from baseline in reflective total ocular symptom scores (TOSS) than those receiving placebo (LS mean difference −0.546; p = 0.008). Significant improvements in ocular symptoms with FFNS versus placebo were also observed for morning pre-dose instantaneous TOSS (LS mean difference −0.519; p = 0.009). FFNS had a favorable safety and tolerability profile: fewer adverse events occurred with FFNS (22%) than with placebo (29%), and no serious adverse events were observed. Conclusions: FFNS 110 μg once daily demonstrated efficacy in relieving both the nasal and ocular symptoms of SAR in adult and adolescent patients. Trial registration: ClinicalTrials.gov identifier: NCT00115622.

Nasal symptoms of allergic rhinitis are an important cause of sleep disturbance. Reduction of nasal symptoms, particularly nasal obstruction, has been linked to improvements in self-reported sleep quality. The enhanced-affinity intranasal corticosteroid fluticasone furoate and the oral antihistamine fexofenadine were compared with respect to nighttime symptoms of seasonal allergic rhinitis. In two randomized, double-blind, double-dummy, parallel-group studies, patients received fluticasone furoate nasal spray (FFNS),110 microg (study 1, n = 312; study 2, n = 224); fexofenadine, 180 mg (study 1, n = 311; study 2, n = 227); or placebo (study 1, n = 313; study 2, n = 229) once daily for 2 weeks. Fluticasone furoate was more effective (p < 0.001) than fexofenadine and placebo in both studies with respect to the mean changes from baseline over the treatment period in the nighttime symptoms score, nighttime reflective total nasal symptom score, predose instantaneous nasal symptom score, and morning peak nasal inspiratory flow. Fluticasone furoate was more effective than placebo (p <or= 0.001) in study 1 and more effective than both placebo and fexofenadine (p <or= 0.034) in study 2 with respect to the mean changes from baseline in the nighttime reflective total ocular symptom score and predose instantaneous total ocular symptom score. In these double-dummy studies, fexofenadine did not separate from placebo in comparisons of the nighttime symptoms score or the nighttime nasal or ocular symptom measures. The incidence of adverse events was similar among groups. FFNS once daily was more effective than fexofenadine and placebo with respect to nighttime sleep disturbance caused by seasonal allergy symptoms.

Fluticasone Furoate Nasal Spray (FFNS), a new enhanced-affinity intranasal corticosteroid, was evaluated against oral fexofenadine (FEX) using the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) to further characterize its therapeutic profile. This was a randomized, double-blind, double-dummy, placebo-controlled, 2-week study (FFU109045) of 936 subjects with SAR who received either FFNS 110 mcg (312 subjects), fexofenadine 180 mg (311), or placebo (313) once-daily. The NRQLQ, a 16-item, self-administered, disease-specific, quality of life instrument that measures functional problems that are most troublesome to subjects with nocturnal allergy symptoms, was administered at randomization and at end of study. NRQLQ items are scored from 0 to 6, with higher scores indicating greater nocturnal impairment. Items are grouped into four domains: sleep problems; sleep time problems; symptoms on waking in the morning; and practical problems. An overall score is calculated from the mean score of all items. Mean change from baseline (MCFB) treatment differences in overall NRQLQ were analyzed using an analysis of covariance model. Baseline NRQLQ global and individual domains scores were similar across treatment groups. MCFB differences in overall NRQLQ scores were significantly (p < 0.001) different with FFNS compared with placebo (-0.6, 95% CI -0.8, 0.1) and FEX (-0.5, 95% CI -0.7, -0.3) MCFB differences between FEX and placebo were not significantly different (-0.1, 95% CI -0.4, 0.1). Subjects treated with FFNS had significant improvements in their rhinitis-related nocturnal quality of life compared with both FEX and placebo, while those treated with FEX did not show significant improvement over placebo.