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Publications (8)22.42 Total impact

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    ABSTRACT: Background The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2-agonist vilanterol (VI) is under development for the treatment of asthma and chronic obstructive pulmonary disease. Objective To compare the efficacy and safety of FF-VI and FF in patients (≥12 years old) with persistent asthma. Methods In a randomized, double-blind, parallel-group study, patients (n = 609) (intent-to-treat population) received FF-VI 100-25 mcg, FF 100 mcg, or placebo once daily (evening) by using a dry powder inhaler for 12 weeks. Coprimary end points were change from baseline in trough FEV1 and serial (0-24 hours) weighted mean FEV1 (wmFEV1). Rescue-free 24-hour periods and safety also were assessed. Results Placebo increased trough FEV1 (196 mL) and wmFEV1 (212 mL) versus baseline. Compared with placebo, FF-VI and FF significantly improved trough FEV1 (172 mL [P < .001] and 136 mL [P = .002]), respectively, and serial wmFEV1 (302 mL [P < .001] and 186 mL [P = .003]), respectively. Treatment differences between FF-VI and FF approached significance for serial wmFEV1 (116 mL; P = .060) but not for trough FEV1 (36 mL; P = .405). The percentage of rescue-free 24-hour periods with FF-VI was 10.6% greater than FF and 19.3% greater than placebo. Statistically significant (P = .032) urinary cortisol suppression was observed with FF-VI (ratio, 0.82) relative to placebo, but not with FF. Adverse event and safety profiles were similar across treatment groups. Conclusions Significant improvement in lung function was observed with FF-VI and FF versus placebo in patients with persistent asthma. Improvement of FEV1 when VI was added to FF was not significant. The high placebo response in evening trough FEV1 may have influenced the assessment of efficacy.
    No preview · Article · Sep 2014
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    ABSTRACT: Background Fluticasone furoate (FF) is a novel, once-daily inhaled corticosteroid (ICS) that has been shown to improve lung function vs. placebo in asthma patients. This study evaluated the efficacy and safety of FF 50 mcg compared with placebo in asthma patients uncontrolled by non-ICS therapy.Methods This 12-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study randomized 248 patients (aged ¿12 years) to once-daily FF 50 mcg administered via the ELLIPTA¿a dry powder inhaler or placebo. The primary endpoint was change from baseline in pre-dose evening trough forced expiratory volume in one second (FEV1). Secondary endpoints were change from baseline in percentage of rescue-free 24-h periods (powered), evening and morning peak expiratory flow, symptom-free 24-h periods and withdrawals due to lack of efficacy. Other endpoints included Asthma Control Test¿, Asthma Quality of Life Questionnaire and ELLIPTA ease of use questions. Safety was assessed throughout the study.ResultsThere was a significant difference in evening trough FEV1 between FF 50 mcg and placebo (treatment difference: 120 mL; p¿=¿0.012). There was also a significant difference in rescue-free 24-h periods (11.6%; p¿=¿0.004) vs. placebo. There were numerically greater improvements with FF vs. placebo for all remaining secondary endpoints. The incidence of adverse events was lower with FF (31%) than with placebo (38%); few were treatment-related (FF 50 mcg: n¿=¿1, <1%; placebo: n¿=¿4, 3%).ConclusionFF 50 mcg once daily significantly improved FEV1 and percentage of rescue-free 24-h periods experienced over 12 weeks vs. placebo, and was well tolerated.Trial registration www.clinicaltrials.gov, registration number: NCT01436071.
    Full-text · Article · Aug 2014 · Respiratory research
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    ABSTRACT: Background Inhaled glucocorticosteroids (ICS) are the mainstay of treatment in asthma. Fluticasone furoate (FF) is a novel, once-daily ICS asthma therapy. This study investigated the efficacy and safety of FF 50mcg in patients with mild to moderate persistent asthma.MethodsA 24-week, multicenter, randomized, placebo- and active-controlled, double-blind, double-dummy, parallel-group, phase III study. 351 patients (aged ≥12 years; uncontrolled by non-ICS therapy) were randomized to treatment (1:1:1) with once-daily FF 50mcg dosed in the evening, twice-daily fluticasone propionate (FP) 100mcg or placebo. The primary endpoint was change from baseline in evening trough forced expiratory volume in 1s (FEV1) at Week 24. Secondary endpoints were change from baseline in the percentage of rescue-free 24h periods (powered endpoint), change from baseline in evening and morning peak expiratory flow, change from baseline in the percentage of symptom-free 24h periods and number of withdrawals due to lack of efficacy.ResultsEvening trough FEV1 at Week 24 was not statistically significantly increased with FF 50mcg once daily (37mL [95% CI: –55, 128]; P=0.430), but was with FP 100mcg twice daily (102mL [10, 194]; P=0.030), versus placebo. No consistent trends were observed across other endpoints, including the powered secondary endpoint. No safety concerns were raised for either active treatment.ConclusionsFP 100mcg twice-daily improved evening trough FEV1 in patients with mild to moderate persistent asthma, but FF 50mcg once–daily did not demonstrate a significant effect. Secondary endpoints showed variable results. No safety concerns were identified for FF or FP.This article is protected by copyright. All rights reserved.
    Preview · Article · Jul 2014 · Allergy
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    ABSTRACT: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS) and vilanterol (VI), a long-acting beta2 agonist, is under development as a once-daily treatment for asthma and chronic obstructive pulmonary disease. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on medium-dose ICS. In a randomized, double-blind, double-dummy, parallel-group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening via dry powder inhaler, or FP/SAL (250/50 μg, n = 403) twice daily via Diskus™/Accuhaler™. The primary efficacy measure was 0-24 h serial weighted mean forced expiratory volume in 1 second (wmFEV1) after 24 weeks of treatment. Improvements from baseline in 0-24 h wmFEV1 were observed with both FF/VI (341 ml) and FP/SAL (377 ml); the adjusted mean treatment difference was not statistically significant (-37 ml [95% confidence interval: -88, 15], p = 0.162). There were no differences between the 0-4 h serial wmFEV1, trough FEV1, and asthma control and quality of life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs, and no treatment-related serious adverse events. The efficacy of once-daily FF/VI was similar to twice-daily FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified. ClinicalTrials.gov; No.: NCT01147848; funded by GSK (HZA113091).
    Full-text · Article · Jul 2013 · Chest
  • Hilary Medley · Socorro Orozco · Ann Allen
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    ABSTRACT: 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. The objective of this study was to estimate the treatment differences (with 95% CI) 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. 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 μg once daily in the morning compared with 100 μg 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. 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 μg once daily in the morning (n = 144), FF Rotadisk 100 μg once daily in the evening (n = 146), FF Rotadisk 250 μg 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 μg once daily in the morning relative to evening was +13.4 L/min (95% CI, 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 μg 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 μg group than placebo. 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 μg appear to be comparable for morning and evening dosing. Clinical.trials.govNCT01499446.
    No preview · Article · Jul 2012 · Clinical Therapeutics
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    ABSTRACT: This randomized, double-blind, multicenter study was designed to evaluate the efficacy of inhaled once-daily fluticasone furoate (FF) administered in the evening in patients with persistent asthma not controlled by short-acting beta(2) agonists, and to determine the dose(s) suitable for further development. Of 1459 patients screened, 598 received one of six treatments: placebo, FF (25 μg, 50 μg, 100 μg or 200 μg) once daily each evening, or fluticasone propionate (FP) 100 μg twice daily for 8 weeks. The primary endpoint was change from baseline in pre-dose evening forced expiratory volume in 1 s (FEV(1)). A dose-response effect was observed for once-daily FF 25-200 μg including (p < 0.001) and excluding placebo (p = 0.03). FF 50-200 μg once daily significantly increased FEV(1) from baseline (p < 0.05 vs placebo), by >200 mL for FF 100 μg and 200 μg. Significant improvements were also achieved for peak expiratory flow, and percentage symptom-free and rescue-free 24 h periods. The magnitude of effect was at least as good as twice-daily FP. Overall, once-daily FF was well tolerated with no systemic corticosteroid effects. FF 50-200 μg/day once daily in the evening demonstrated dose-related efficacy in asthma with 100-200 μg appearing to be the optimal doses for further evaluation. ClinicalTrials.gov: NCT00603382.
    Preview · Article · Feb 2012 · Respiratory medicine

  • No preview · Conference Paper · May 2011

  • No preview · Conference Paper · May 2011