Hilary Medley

Efficacy and Safety of Fluticasone Furoate/Vilanterol Compared With Fluticasone Propionate/Salmeterol Combination in Adult and Adolescent Patients With Persistent Asthma: A Randomized Trial

Background: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. 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 a medium dose of ICS. Methods: 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 delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment. Results: Improvements from baseline in 0- to 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% CI, −88 to 15, P = 0.162). There were no differences between 0- to 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. Conclusions: The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified. Trial registry: ClinicalTrials.gov; No.: NCT01147848; URL: www.clinicaltrials.gov

Fluticasone propionate 50 μg BID versus 100 μg BID in the treatment of children with persistent asthma

Abstract The aim of this multicenter, double-masked study was to compare the efficacy and safety of two different doses of inhaled fluticasone propionate dry powder—50 μg and 100 μg—administered BID via a multidose powder inhaler with those of placebo in the treatment of children with persistent asthma. After a 2-week run-in period, 263 patients were randomized to treatment with twice-daily placebo (n = 92), fluticasone 50 μg (n = 85), or fluticasone 100 μg (n = 86) for 12 weeks. One hundred sixty-six (63%) patients were male, and 224 (85%) were white, with a mean age of 8 years. Two hundred twenty-one (84%) patients were atopic, and 167 (63%) had been asthmatic for 1 to 5 years. Baseline mean morning peak expiratory flow (PEF) values were 207 L/min, 199 L/min, and 194 L/min, and baseline percentages of predicted normal values were 86%, 80%, and 81% for the groups receiving placebo, fluticasone 50 μg, and fluticasone 100 μg, respectively. At the end of the first week of treatment, patients in both fluticasone groups had significantly greater improvements in morning PEF than did those receiving placebo. Patients experienced mean increases of 4 L/min, 22 L/min, and 26 L/min with placebo, fluticasone 50 μg, and fluticasone 100 μg, respectively. At the end point (the last evaluable visit), patients in both fluticasone groups continued to have significantly greater improvements in morning PEF than did patients receiving placebo. Patients experienced mean increases of 17 L/min, 50 L/min, and 57 L/min with placebo, fluticasone 50 μg, and fluticasone 100 μg, respectively. Changes in the percentage of predicted values by end point were 8%, 20%, and 26% with placebo, fluticasone 50 μg, and fluticasone 100 μg, respectively. The probability of remaining in the study, according to predefined withdrawal criteria, indicated a significant treatment difference in favor of fluticasone. Withdrawal criteria were met by 63%, 42%, and 29% of patients receiving placebo, fluticasone 50 μg, and fluticasone 100 μg, respectively. This study clearly demonstrates the superiority of fluticasone 50 and 100 μg BID over placebo in the treatment of persistent asthma in children.

Fluticasone Furoate–Vilanterol 100-25 mcg Compared with Fluticasone Furoate 100 mcg in Asthma: A Randomized Trial

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 (wmFEV(1)). Rescue-free 24-hour periods and safety also were assessed. RESULTS Placebo increased trough FEV1 (196 mL) and wmFEV(1) (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 wmFEV(1) (302 mL [P < .001] and 186 mL [P = .003]), respectively. Treatment differences between FF-VI and FF approached significance for serial wmFEV(1) (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.

Once-daily fluticasone furoate 50 mcg in mild-to-moderate asthma: a 24-week placebo-controlled randomized trial.

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 50 mcg in patients with mild‐to‐moderate persistent asthma.

Efficacy and safety profile of fluticasone furoate administered once daily in the morning or evening: a randomized, double-blind, double-dummy, placebo-controlled trial in adult and adolescent patients with persistent bronchial asthma.

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% 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. 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 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. 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 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. 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 μg appear to be comparable for morning and evening dosing. Clinical.trials.govNCT01499446.