BACKGROUND:Depemokimab, the first ultra-long-acting biologic with enhanced IL-5 binding affinity, high inhibition potency, and extended half-life, enables twice-yearly dosing in patients with asthma. In phase III SWIFT-1/-2 trials, depemokimab significantly reduced the annualized exacerbation rate by 54% versus placebo with sustained suppression of inflammation assessed by blood eosinophil count in type 2 asthma. OBJECTIVE:To evaluate the onset and duration of depemokimab efficacy across each 26-week dosing period in the pooled SWIFT-1/-2 population and identify patient characteristics associated with enhanced clinical response. METHODS:Patients with type 2 asthma, independent of Asthma Control Questionnaire-5 (ACQ-5) status, were randomized 2:1 to receive depemokimab 100 mg subcutaneously or placebo every 26 weeks for 52 weeks. Prespecified end points included time to first exacerbation, St George's Respiratory Questionnaire total score, ACQ-5 score, Asthma Nighttime Symptom Diary weekly score, Asthma Daytime Symptom Diary weekly score, and rescue medication use over time. We conducted post hoc subgroup analyses by baseline characteristics. RESULTS:Depemokimab reduced the probability of first exacerbation over 52 weeks versus placebo by 46% (hazard ratio = 0.54; 95% CI, 0.43-0.69), with effects from week 4 sustained across both dosing periods. Annualized exacerbation rate reductions were most pronounced in patients with asthma disease duration less than 10 years, comorbid chronic rhinosinusitis with nasal polyps, and medium-dose inhaled corticosteroids (ICS) at baseline. Across each dosing period, depemokimab also improved St George's Respiratory Questionnaire, ACQ-5, Asthma Nighttime Symptom Diary, and Asthma Daytime Symptom Diary scores, particularly in patients with baseline ACQ-5 scores of 1.5 or greater, with sustained improvements in rescue medication. CONCLUSION:Early and sustained efficacy with depemokimab was observed across 26-week dosing periods in type 2 asthma, with enhanced benefits in patients with shorter disease duration who had not progressed to high-dose ICS.

Rationale: Depemokimab is the first ultra-long-acting biologic engineered with enhanced interleukin-5 binding affinity, high inhibition potency, and an extended half-life, enabling twice-yearly dosing in patients with asthma. In the Phase III SWIFT-1/2 studies, depemokimab treatment significantly reduced the annualized exacerbation rate by 54% with sustained inhibition of type 2 inflammation observed in patients with type 2 asthma characterized by blood eosinophils.1 The reduced dosing schedule offered by depemokimab may alleviate treatment burden; these pooled analyses of the SWIFT-1/2 studies explore how depemokimab efficacy is maintained over the extended dosing interval. Methods: Patients with asthma and blood eosinophil counts ≥150 cells/µl at screening or ≥300 cells/µl in the past year receiving medium-to-high dose inhaled corticosteroids were randomized 2:1 to receive depemokimab 100 mg subcutaneous or placebo every 26 weeks for 52 weeks.Patients with any baseline Asthma Control Questionnaire-5 score were eligible. Prespecified secondary endpoints included change from baseline to Week 52 in total St George's Respiratory Questionnaire (SGRQ); prespecified other endpoints included time to first exacerbation. No multiplicity adjustments were performed in these pooled analyses. Results: Full analysis populations for the SWIFT-1/2 studies included 762 patients (depemokimab, n=502; placebo, n=260). Mean (standard error) change from baseline in total SGRQ score was numerically greater for depemokimab versus placebo at Week 4 (-10.79 [0.669] vs -8.02 [0.928]) and was maintained at Weeks 26 (-11.94 [0.763] vs -9.73 [1.054]) and 52 (-13.92 [0.758] vs -11.04 [1.055]; Figure A). This finding was consistent across the individual domains, which constitute SGRQ total score (i.e., symptoms, activity, and impacts) and sustained over time. The probability of experiencing an exacerbation with depemokimab was lower than with placebo by Week 4. This difference was maintained through Week 52, with no increased exacerbation risk observed in the weeks prior to dosing at Week 26 and 52 (Figure B). The probability of having an exacerbation (95% confidence interval [CI]) over 52 weeks was 32% (28%, 37%) with depemokimab and 49% (43%, 55%) with placebo (hazard ratio [95% CI] 0.54 [0.43, 0.69]).Conclusions: Twice-yearly depemokimab treatment was associated with numerically greater benefits compared with placebo, sustained over the depemokimab dosing interval, in overall health and risk of exacerbations in patients with type 2 asthma. The finding of this pooled analysis of the SWIFT-1/2 studies supports the sustained inhibition of type 2 inflammation by depemokimab. Reference: 1. Jackson DJ et al. NEJM 2024;10.1056/NEJMoa2406673.

BACKGROUND:Limited data exist comparing inhaled corticosteroid (ICS) plus adjunctive therapy vs ICS alone in pediatric asthma patients. OBJECTIVE:To evaluate the efficacy and safety of fluticasone furoate/vilanterol (FF/VI) vs FF in children and adolescents with asthma. METHODS:This phase 3, randomized, double-blind, multicenter study (NCT03248128) included participants aged 5 to 17 years with six months or more asthma history uncontrolled on ICS monotherapy. Participants received 4-week open-label fluticasone propionate (100 µg) twice daily before 1:1 randomization to 24-week double-blind FF (50 µg:100 µg) or FF/VI (50/25 µg:100/25 µg) once daily. Two populations with different primary endpoints were analyzed to meet United States (week 12 weighted mean forced expiratory volume in 1 second [FEV1; 0-4 hours]; participants aged 5-17 years) and European (change from baseline predose morning peak expiratory flow [ΔAM PEF] averaged over weeks 1-12; participants aged 5-11 years) regulatory requirements. RESULTS:Overall, 902 participants, including 673 children aged 5 to 11 years, were randomized and treated. In participants aged 5 to 17, week 12 weighted mean FEV1 (0-4 hours) was greater with FF/VI vs FF (difference: 0.083 L; P < .001). In participants aged 5 to 11, ΔAM PEF over weeks 1 to 12 showed numerical improvement with FF/VI vs FF but was not statistically significant (difference: 3.2 L/min; P = .228). No drug-related serious adverse events or deaths were reported. CONCLUSION:FF/VI significantly improved weighted mean FEV1 (0-4 hours; participants aged 5-17 years), but not ΔAM PEF (participants aged 5-11 years) vs FF. No new safety concerns were apparent. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03248128.

Clinical Implications In clinical practice, attention to high or rising reliever use may help prevent exacerbations, by prompting patients to implement their action plan and reminding them to take their regular controller therapy. If reliever data were available in real-time, they could alert the patient and/or clinician to an impending exacerbation, and could identify patients with ongoing high reliever use, who may be at greater risk of exacerbation.

Background: This analysis from the 6-month AUSTRI study (GSK115359, n=11,679) explored the rate and heterogeneity of severe exacerbations with fluticasone propionate (FP) alone compared with FP plus salmeterol (FSC) in patients aged ≥12 years with persistent asthma and a 1-year history of exacerbations. Methods: Primary cause of severe exacerbation was grouped as: environmental, allergic, infective and other. Patient characteristics according to exacerbation (yes/no), primary cause, and period before and after events (Day -14 to +14) vs a corresponding 29-day period in non-exacerbating patients, were analysed post-hoc. Results: 1077 (9.2%) patients reported ≥1 severe exacerbation during study. Exacerbation cause was recorded as environmental for 14.3% of exacerbations, allergic for 8.4%, and infective for 45.3%. Rate of asthma exacerbations was significantly reduced by 21.8% (Ratio: 0.782; 95% CI: 0.691-0.886) for FSC vs FP patients. In patients with exacerbation, mean rescue use (puffs/day) increased from 1.5 (Day -14) to 3.2 (Day 1) and back to 1.5 (Day +14), compared with mean 0.8 puffs/day in non-exacerbating patients (Fig. 1). Conclusions: In patients with a history of severe asthma exacerbations, regular twice-daily dosing with FSC was associated with a lower rate of asthma exacerbations compared with FP. Rescue medication use was higher pre- and post-exacerbation than the average for non-exacerbating patients. Funding: GSK (ID 213505)

Objective: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV1) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. Methods: A randomized, double-blind, crossover study was conducted in patients (aged 12-50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 mu g BD), patients with a >= 20% decrease in postexercise FEV1 received FF/VI 100/25 mu g OD or FP 250 mu g BD for 2 weeks. Exercise challenges were carried out 23 h after the first dose of study medication, and 12 and 23 h after evening clinic dose at the end of the 2-week treatment period. After a 2-week washout period (FP 250 mu g), patients crossed over treatments, with procedures and tests repeated. The primary endpoint was mean maximal percentage decrease from pre-exercise FEV1 following exercise challenge 12-h postevening dose on Day 14. Results: The mean maximal percentage decrease from pre-exercise FEV1 after the 12-h exercise challenge (Day 14) was 15.02% with FF/VI, and 16.71% with FP (difference, -1.69; 95% confidence interval, -3.76 to 0.39; p = 0.109). After the 23-h exercise challenge (Day 14), respective mean maximal decreases were 11.90% and 14.05% (difference, -2.15; 95% confidence interval, -4.31 to 0.01). Conclusion: The study failed to show a difference between FF/VI and FP at providing long-term protection from exercise-induced bronchoconstriction.

Objective: Symptoms, including night-time awakenings, affect the quality of life of people with asthma. Fluticasone furoate/vilanterol (FF/VI) reduces exacerbations, improves lung function, and rescue-free and symptom-free 24-hour periods in patients with asthma. These post hoc analyses compared daytime and night-time symptoms in patients with asthma who received FF/VI, versus FF, fluticasone propionate (FP) or placebo. Methods: Daytime and night-time symptoms were collected via electronic daily diary cards in three Phase III randomized studies of once-daily FF/VI in patients with uncontrolled asthma on inhaled corticosteroids (ICSs) +/- long-acting beta(2) agonists (n = 609/1039/586). Endpoints included change from baseline in symptom-free days and nights (analyzed by Analysis of Covariance, covariates: baseline, region, sex, age, and treatment), time for patients to achieve seven consecutive symptom-free nights (analyzed by Cox proportional hazards' model, covariates as above), and proportion of patients experiencing 100% symptom-free nights per week (analyzed by logistic regression, covariates: percentage of symptom-free nights, sex, age, and treatment). Results: Improvements in symptom-free days and nights were generally observed for all treatments. More patients who received FF/VI experienced 100% symptom-free nights in the last week of the treatment period than patients who received ICS alone or placebo. FF/VI also reduced time to achieve seven consecutive symptom-free nights. Patients with at least one night of symptoms at baseline experienced an additional 2.7 and 2.0 symptom-free nights per week with FF/VI 100/25 mu g, versus 1.9 and 1.7 with FF alone; similar findings were seen with FF/VI 200/25 mu g. Conclusions: Benefits in terms of symptom-free days and nights were observed for patients receiving FF/VI versus comparators in these post hoc analyses.

Objective: We aimed to demonstrate non-inferiority of once-daily fluticasone furoate/vilanterol 100/25 µg (FF/VI) to twice-daily fluticasone propionate/salmeterol 250/50 µg (FP/SAL) in adults/adolescents with asthma well controlled on inhaled corticosteroid/long-acting β2 agonist (ICS/LABA). Methods: This was a randomized, double-blind, double-dummy, parallel-group, 24-week study (NCT02301975/GSK study 201378). Patients whose asthma met study-defined criteria for control were randomized 1:1:1 to receive FF/VI, FP/SAL or twice-daily FP 250 µg for 24 weeks. Primary endpoint was change from baseline in evening trough forced expiratory volume in 1 second (FEV1). Secondary endpoints included rescue-/symptom-free 24-hour periods. Safety was also assessed. Results: The intent-to-treat (ITT) population included 1504 randomized and treated patients (504 FF/VI; 501 FP/SAL; 499 FP); mean age 43.5 years, 64% female. FF/VI demonstrated non-inferiority (using a margin of −100 mL) to FP/SAL for evening trough FEV1 at Week 24 (ITT: 19 mL [95% confidence interval (CI) −11 to 49]; per protocol population [N = 1336]: 6 mL [95% CI −27 to 40]). Improvement in evening trough FEV1 at Week 24 for both FF/VI (123 mL; p < 0.001) and FP/SAL (104 mL; p < 0.001) was greater than FP. FF/VI increased rescue-/symptom-free 24-hour periods by 1.2%/1.2% compared with FP/SAL. All treatments were well tolerated. On-treatment adverse event (AE) rates were 43% to 45% across arms; there were no drug-related serious AEs. Conclusions: FF/VI was non-inferior to FP/SAL for evening trough FEV1 at 24 weeks. These data suggest that patients well controlled on FP/SAL could step across to FF/VI without loss of control.

SESSION TITLE: Respiratory Care SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 08:45 AM - 10:00 AM PURPOSE: The objective of this study was to demonstrate non-inferiority of furoate (FF)/vilanterol (VI) Ellipta 100/25 once daily (QD) to propionate (FP)/salmeterol (SAL) Diskus 250/50 twice daily (BID) in adult and adolescent subjects 12 years of age and older with persistent asthma, adequately controlled on twice daily inhaled corticosteroid (ICS)/long acting β2-agonist (LABA) at a dose equivalent to FP/SAL 250/50 mcg BID. METHODS: This was a randomised, double-blind, double-dummy, parallel-group 24-week study. Patients whose asthma was controlled, in the opinion of their physician, on a BID ICS/LABA entered a 5 day LABA washout period receiving ICS only, followed by reversibility testing. Patients who met reversibility criteria (≥150mL improvement in FEV1 post salbutamol/albuterol) at the end of LABA washout entered a 4 week run-in period using open-label FP/SAL 250/50 BID. At the end of this run-in period, patients whose asthma met study defined criteria for control were randomised 1:1:1 to receive FF/VI 100/25 QD (dosed in the evening), FP/SAL 250/50 BID, or FP 250 BID for 24 weeks. Primary endpoint was change from baseline in evening trough FEV1. Secondary endpoints included rescue-free 24-hour periods. Safety was also assessed. RESULTS: 1504 patients were randomised and treated and comprised the Intent-to-Treat (ITT) Population; 504 to FF/VI, 501 to FP/SAL and 499 to FP; 1336 of these were included in the Per protocol (PP) Population. 1426 (95%) patients completed the study. Mean age in years was 43.5 and percentage of females was 64%. Mean pre-bronchodilator percent predicted FEV1 was 90.24% at baseline. Non-inferiority in evening trough FEV1 (lower bound of 95% CI greater than the pre-defined non-inferiority margin of -100mL) of FF/VI 100/25 to FP/SAL 250/50 was demonstrated at week 24 (19mL, 95% CI -11, 49 for ITT Population and 6mL, 95% CI -27, 40 for PP Population). Evening trough FEV1 for both FF/VI (123mL, p<0.001) and FP/SAL (104mL, p<0.001) was significantly greater than FP. The adjusted mean change in rescue-free 24-hour periods for FF/VI was comparable to FP/SAL (1.2%, 95% CI -0.5, 3.0). FF/VI increased rescue-free 24-hour periods by 2.7% compared with FP (p=0.002) and FP/SAL by 1.4% (p=0.106) compared with FP. All treatments were well tolerated with similar rates of on-treatment adverse events across the treatment groups (FF/VI 45%, FP/SAL 43%, and FP 44%) and no treatment-related serious adverse events. CONCLUSIONS: FF/VI demonstrated non-inferiority to FP/SAL on evening trough FEV1 in this population of controlled asthmatics. Assay sensitivity was demonstrated with FF/VI and FP/SAL being significantly superior to FP. The adverse event profile of FF/VI is consistent with the adverse event profile of ICS/LABAs. CLINICAL IMPLICATIONS: This study demonstrates that patients whose asthma is currently well controlled on twice daily FP/SAL can step across to once daily FF/VI without loss of control. Funded by GSK (201378, NCT02301975). DISCLOSURE: David Bernstein: Consultant fee, speaker bureau, advisory committee, etc.: GSK, Other: PI in GSK sponsored clinical trials Richard Forth: Employee: GSK, Shareholder: GSK Louisa Yates: Employee: GSK, Shareholder: GSK Leslie Andersen: Employee: GSK Loretta Jacques: Employee: GSK, Shareholder: GSK No Product/Research Disclosure Information

Introduction and objectives FF/VI, the first once daily inhaled corticosteroid/long-acting ß2-agonist combination available for the treatment of asthma, has demonstrated a sustained 24 hour improvement in lung function and improvement in symptom-free 24 hour periods. Methods Post-hoc analyses of diary card data from three Phase III studies were performed to examine whether there was an improvement in night-time awakening during the studies for those patients treated with the addition of vilanterol to fluticasone furoate. The diary card scale used is described below. Changes in night-time awakenings over the duration of the studies were analysed for percentage of patients with ≥50% symptom-free nights, including the time taken for 50% of patients to achieve 7 nights without symptoms. Night-time Symptom Score: 0 = No symptoms during the night 1 = Symptoms causing me to wake once (or wake early) 2 = Symptoms causing me to wake twice or more (including waking early) 3 = Symptoms causing me to be awake for most of the night 4 = Symptoms so severe that I did not sleep at all To be counted as symptom-free during the night the patient needed to record a score of 0. Results The percentage of patients with ≥50% symptom-free nights was generally higher in patients treated with FF/VI compared to either FF or FP alone (Table below). The time (in days) for 50% of patients to achieve 7 nights without symptoms was achieved sooner with patients treated with FF/VI compared to FF alone (Table). Conclusions In general, night-time awakenings improved over time in asthma patients with FF/VI and improved faster with FF/VI compared with FF or placebo.

Introduction and objectives FF/VI is the first once daily inhaled corticosteroid/long-acting b2-agonist combination available for the treatment of asthma. Data from five phase III studies that have previously been presented have generally demonstrated a sustained 24 h improvement in lung function and improvement in rescue-free 24 h periods compared with placebo (P), FF alone or fluticasone propionate (FP). Due to differences in study comparators, duration of study and primary endpoints, integration of the study results has not been possible therefore each study is considered separately. Methods Post-hoc analyses of diary card data from the 5 studies were performed to examine whether there was any difference in the contribution of the day and night time rescue medication use to the 24 h rescue-free period. Patients recorded in an electronic diary card the number of inhalations of rescue salbutamol/albuterol inhalation aerosol used during the day and night. To be counted as rescue-free during the day or night the patient needed to record a no use of rescue medication during that period. Results The post-hoc analyses demonstrated that the improvements in day and night time rescue –free periods were similar to the 24 h rescue free periods. See Figure 1 below.Abstract P155 Figure 1 Conclusions In general the benefit of FF/VI on rescue free 24 h periods is reflected in the improvements seen in day and night time rescue use.

The authors regret that an error occurred in Table 2 in the above-mentioned article. The data on the fourth row of the table, labelled "Morning PEF (l/min): difference in LS mean change from baseline (95% CI) over weeks 1–24", should read as follows:•FF100 μg OD vs. placebo: 12.1 (4.0, 20.2)•FP250 μg BD vs. placebo: 7.6 (−0.5, 15.7) This amendment does not materially affect the findings or interpretations presented in the manuscript. The authors would like to apologise for any inconvenience caused. Efficacy and safety of fluticasone furoate 100 μg once-daily in patients with persistent asthma: A 24-week placebo and active-controlled randomised trialRespiratory MedicineVol. 108Issue 1PreviewInhaled corticosteroids (ICSs) improve asthma disease control; once-daily ICS administration may have advantages for patients. Our objective was to assess the efficacy and safety of the novel ICS fluticasone furoate (FF) over 24 weeks versus placebo. This was a 24-week double-blind, double-dummy, placebo- and active-controlled study ( NCT01159912 ) of 343 asthma patients (≥12 years) not controlled by their current ICS. Patients were randomised (1:1:1) to FF100 μg, placebo (both administered once-daily [OD] via ELLIPTA™ dry powder inhaler in the evening) or fluticasone propionate (FP) 250 μg (administered twice-daily (BD) via DISKUS™/ACCUHALER™). Full-Text PDF Open Access

Rationale: The efficacy of FF and FF/VI have been studied in moderate/severe asthma. This analysis examined the effect of baseline eos level on response to different doses of FF and FF/VI. Methods: In post-hoc analyses of 2 studies (Woodcock A. et al. BMC Pulm Med 2014;14:113; Bernstein D.I. et al. Am J Respir Crit Care Med 2014:A6671; FFA114496: NCT01431950 & HZA116863: NCT01686633) that compared 2 doses of FF and FF/VI, patients were grouped by their baseline blood eos level (≤0.15GI/L or >0.15GI/L) and the effect on trough and weighted mean FEV1, and asthma control test (ACT) was analysed. Results: The table summarises the effects of FF and FF/VI on the endpoints in the 2 subgroups of patients at the end of the study. Conclusion: Across both studies, there was a trend towards greater lung function effects with the higher dose of FF or FF/VI in patients with a higher baseline eos level.

Introduction and objectives FF/VI is the first once daily inhaled corticosteroid/long-acting b2-agonist combination available for the treatment of asthma. Results from five phase III studies that have previously been presented demonstrated a sustained 24 h improvement in lung function and improvement in symptom-free 24 h periods. Methods Post-hoc analyses of diary card data from these studies were performed to examine whether there was any difference in the contribution of the day and night time symptom-free period to the 24 h symptom-free period. The diary card scale used is described below. Day-time Symptom Score: 0 = No symptoms during the day 1 = Symptoms for one short period during the day 2 = Symptoms for two or more short periods during the day 3 = Symptoms for most of the day which did not affect my normal daily activities 4 = Symptoms for most of the day which did affect my normal daily activities 5 = Symptoms so severe that I could not go to work or perform normal daily activities Night-time Symptom Score: 0 = No symptoms during the night 1 = Symptoms causing me to wake once (or wake early) 2 = Symptoms causing me to wake twice or more (including waking early) 3 = Symptoms causing me to be awake for most of the night 4 = Symptoms so severe that I did not sleep at all To be counted as symptom-free during the day or night the patient needed to record a score of 0. Results The post-hoc analyses demonstrated that the improvements in day and night time symptom –free periods were similar to the 24 h symptom free periods. See Figure 1 below. Conclusions In general benefits in symptom free days and symptom free nights contributed to the benefit of FF/VI over comparator groups in terms of 24 h symptom free periods.

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.

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 50 mcg in patients with mild-to-moderate persistent asthma.METHODS:A 24-week, multicenter, randomized, placebo-controlled and active-controlled, double-blind, double-dummy, parallel-group phase III study. Three hundred and fifty-one patients (aged ≥12 years; uncontrolled by non-ICS therapy) were randomized to treatment (1 : 1 : 1) with once-daily FF 50 mcg dosed in the evening, twice-daily fluticasone propionate (FP) 100 mcg or placebo. The primary endpoint was change from baseline in evening trough forced expiratory volume in 1 s (FEV1 ) at Week 24. Secondary endpoints were change from baseline in the percentage of rescue-free 24-h periods (powered endpoint), change from baseline in evening and morning peak expiratory flow, change from baseline in the percentage of symptom-free 24-h periods and number of withdrawals due to lack of efficacy.RESULTS:Evening trough FEV1 at Week 24 was not statistically significantly increased with FF 50 mcg once-daily (37 ml [95% CI: -55, 128]; P = 0.430), but was with FP 100 mcg twice daily (102 ml [10, 194]; P = 0.030), vs placebo. No consistent trends were observed across other endpoints, including the powered secondary endpoint. No safety concerns were raised for either active treatment.CONCLUSIONS:FP 100 mcg twice daily improved evening trough FEV1 in patients with mild-to-moderate persistent asthma, but FF 50 mcg once daily did not demonstrate a significant effect. Secondary endpoints showed variable results. No safety concerns were identified for FF or FP.