patients aged  12 years with asthma were eligible if they could demonstrate a  12% and  200-ml reversibility of fev1 following albuterol inhalation at screening and had a best evening fev1 of 40% to 85% of the predicted normal value at screening and at randomization . before screening
, patients had been taking ics for  12 weeks , with a stable medium dose of ics ( fp 250 g bid or equivalent ) for  4 weeks .
the study was approved by the local ethics review committees ( e - table 1 ) and was conducted in accordance with the declaration of helsinki and good clinical practice guidelines .
this phase 3 , multicenter , randomized , double - blind , double - dummy , parallel group study was conducted between june 16 , 2010 , and july 27 , 2011 . after screening
, eligible patients entered a 4-week run - in period during which they replaced their current asthma medication with fp 250 g bid , and their short - acting bronchodilator with albuterol delivered through a metered - dose inhaler .
after the run - in period , patients received ( 1:1 ) either ff / vi 100/25 g ( emitted dose , 92/22 g ) once daily in the evening , administered through an ellipta dry powder inhaler ( glaxosmithkline ) , or fp / sal 250/50 g bid ( morning and evening ) through diskus / accuhaler ( glaxosmithkline ) for 24 weeks . the central randomization schedule was generated by the sponsor with a validated computerized system ( randall ; glaxosmithkline ) .
compliance with study medication was measured by reviewing the dose counter on the dry powder inhaler and diskus / accuhaler .
the primary end point was change from baseline in 0- to 24-h serial weighted mean ( wm ) fev1 after 24 weeks of treatment .
secondary end points were individual serial fev1 assessments at week 24 ( fev1 at each time point on day 168 ) , time to onset of bronchodilator effect ( the time point when fev1 first exceeded the 12% and 200-ml increase over baseline [ taken from serial measurements ] ) at randomization visit only , 0- to 4-h serial wmfev1 postdose at the randomization visit and at week 24 , percentage of patients experiencing a  12% and  200-ml increase from baseline in fev1 at 12 and 24 h at week 24 , and change from baseline in clinic visit trough ( prebronchodilator and predose ) fev1 at week 24 .
other efficacy end points were scores on the asthma quality of life + 12 questionnaire ( aqlq+12 ) , the asthma control test , and the european quality of life-5 dimensions ( eq-5d ) test , and unscheduled health - care resource utilization .
a post hoc analysis of the individual aqlq+12 domains and minimally important difference (  0.5-point improvement in aqlq+12 score ) was also performed .
other safety assessments were 24-h urinary cortisol ( uc ) excretion at baseline and at the end of the 24-week treatment period ( subset of patients ) ; vital signs ( diastolic and systolic bp , pulse rate ) ; incidence of severe asthma exacerbations ; liver safety ; and ecg , clinical chemistry , and hematology screening assessments .
patients were withdrawn from the study because of lack of efficacy if they experienced a severe exacerbation or worsening of asthma or at the investigator s discretion .
a severe exacerbation was defined as deterioration of asthma requiring treatment with systemic or oral corticosteroids for  3 days or an inpatient hospitalization or ed visit that required systemic corticosteroids .
worsening asthma was defined as a requirement for any treatment other than study medication or use of rescue albuterol .
severe asthma exacerbations were not recorded as an ae unless they met the definition of a serious adverse event ( sae ) .
sample size calculations were based on the primary end point of 0- to 24-h serial wmfev1 at the end of the 24-week treatment period for the treatment comparison of ff / vi 100/25 g once daily vs fp / sal 250/50 g bid .
it was estimated that approximately 348 patients with evaluable data per treatment group would provide 90% power to detect a difference of 80 ml between ff / vi 100/25 g and fp / sal 250/50 g ; this assumed an sd of 325 ml .
details about the analysis populations and power calculation are provided in e - appendix 4 .
the primary analysis was performed on the intention - to - treat population with an analysis of covariance model allowing for the effects of baseline fev1 , region , sex , age , and treatment group .
a two - sided 5% risk ( significance level ) associated with incorrectly rejecting the null hypothesis was considered acceptable for this study . for the secondary and other efficacy end points ,
if the statistical test for the primary end point failed to reject the null hypothesis of no treatment difference at the 0.05 significance level , the tests for the secondary and other efficacy end points were to be interpreted as descriptive only .
as a consequence of site audits conducted by the study sponsor glaxosmithkline , concerns about the quality of data supplied were identified for two study centers .
these centers contributed 57 patients ( 7% of enrolled patients ) to the study . because of these concerns , analysis of the primary end point was repeated , excluding the data from these two centers .
the authors and study sponsor are satisfied that the exclusion of data derived from these centers did not materially change the findings of the study ; therefore , we present a complete data set from all the centers .
patients aged  12 years with asthma were eligible if they could demonstrate a  12% and  200-ml reversibility of fev1 following albuterol inhalation at screening and had a best evening fev1 of 40% to 85% of the predicted normal value at screening and at randomization . before screening
, patients had been taking ics for  12 weeks , with a stable medium dose of ics ( fp 250 g bid or equivalent ) for  4 weeks .
the study was approved by the local ethics review committees ( e - table 1 ) and was conducted in accordance with the declaration of helsinki and good clinical practice guidelines .
this phase 3 , multicenter , randomized , double - blind , double - dummy , parallel group study was conducted between june 16 , 2010 , and july 27 , 2011 . after screening , eligible patients entered a 4-week run - in period during which they replaced their current asthma medication with fp 250 g bid , and their short - acting bronchodilator with albuterol delivered through a metered - dose inhaler .
after the run - in period , patients received ( 1:1 ) either ff / vi 100/25 g ( emitted dose , 92/22 g ) once daily in the evening , administered through an ellipta dry powder inhaler ( glaxosmithkline ) , or fp / sal 250/50 g bid ( morning and evening ) through diskus / accuhaler ( glaxosmithkline ) for 24 weeks .
the central randomization schedule was generated by the sponsor with a validated computerized system ( randall ; glaxosmithkline ) .
compliance with study medication was measured by reviewing the dose counter on the dry powder inhaler and diskus / accuhaler .
the primary end point was change from baseline in 0- to 24-h serial weighted mean ( wm ) fev1 after 24 weeks of treatment .
secondary end points were individual serial fev1 assessments at week 24 ( fev1 at each time point on day 168 ) , time to onset of bronchodilator effect ( the time point when fev1 first exceeded the 12% and 200-ml increase over baseline [ taken from serial measurements ] ) at randomization visit only , 0- to 4-h serial wmfev1 postdose at the randomization visit and at week 24 , percentage of patients experiencing a  12% and  200-ml increase from baseline in fev1 at 12 and 24 h at week 24 , and change from baseline in clinic visit trough ( prebronchodilator and predose ) fev1 at week 24 .
other efficacy end points were scores on the asthma quality of life + 12 questionnaire ( aqlq+12 ) , the asthma control test , and the european quality of life-5 dimensions ( eq-5d ) test , and unscheduled health - care resource utilization .
patients were asked to complete questionnaires at baseline and end of treatment . a post hoc analysis of the individual aqlq+12 domains and minimally important difference (  0.5-point improvement in aqlq+12 score ) was also performed .
other safety assessments were 24-h urinary cortisol ( uc ) excretion at baseline and at the end of the 24-week treatment period ( subset of patients ) ; vital signs ( diastolic and systolic bp , pulse rate ) ; incidence of severe asthma exacerbations ; liver safety ; and ecg , clinical chemistry , and hematology screening assessments .
patients were withdrawn from the study because of lack of efficacy if they experienced a severe exacerbation or worsening of asthma or at the investigator s discretion .
a severe exacerbation was defined as deterioration of asthma requiring treatment with systemic or oral corticosteroids for  3 days or an inpatient hospitalization or ed visit that required systemic corticosteroids .
worsening asthma was defined as a requirement for any treatment other than study medication or use of rescue albuterol .
severe asthma exacerbations were not recorded as an ae unless they met the definition of a serious adverse event ( sae ) .
sample size calculations were based on the primary end point of 0- to 24-h serial wmfev1 at the end of the 24-week treatment period for the treatment comparison of ff / vi 100/25 g once daily vs fp / sal 250/50 g bid .
it was estimated that approximately 348 patients with evaluable data per treatment group would provide 90% power to detect a difference of 80 ml between ff / vi 100/25 g and fp / sal 250/50 g ; this assumed an sd of 325 ml .
details about the analysis populations and power calculation are provided in e - appendix 4 .
the primary analysis was performed on the intention - to - treat population with an analysis of covariance model allowing for the effects of baseline fev1 , region , sex , age , and treatment group . a two - sided 5% risk ( significance level ) associated with incorrectly rejecting the null hypothesis
was considered acceptable for this study . for the secondary and other efficacy end points ,
if the statistical test for the primary end point failed to reject the null hypothesis of no treatment difference at the 0.05 significance level , the tests for the secondary and other efficacy end points were to be interpreted as descriptive only .
as a consequence of site audits conducted by the study sponsor glaxosmithkline , concerns about the quality of data supplied were identified for two study centers .
these centers contributed 57 patients ( 7% of enrolled patients ) to the study . because of these concerns , analysis of the primary end point was repeated , excluding the data from these two centers .
the authors and study sponsor are satisfied that the exclusion of data derived from these centers did not materially change the findings of the study ; therefore , we present a complete data set from all the centers .
most patients ( 89% ) in both treatment groups completed the 24-week treatment period ( fig 1 ) .
ae = adverse event ; bd = twice daily ; ff = fluticasone furoate ; fp = fluticasone propionate ; itt = intention to treat ; od = once daily ; sal = salmeterol ; vi = vilanterol .
main reason was that patients did not meet inclusion / exclusion criteria ( n = 613 [ 39% ] ) .
main reason was that patients did not meet continuation criteria ( n = 103 [ 7% ] ) .
patient demographics and baseline lung function ( intention - to - treat population ) data are presented as mean  sd or no .
ff = fluticasone furoate ; fp = fluticasone propionate ; ics = inhaled corticosteroid ; laba = long - acting 2-agonist ; od = once daily ; sal = salmeterol ; vi = vilanterol .
patients needed to have been maintained on a medium dose of ics ( eg , fp 250 g bid ) for  4 wk before screening .
improvements from baseline in 0- to 24-h serial wmfev1 were seen with both ff / vi ( 341 ml ) and fp / sal ( 377 ml ) ; however , the adjusted mean treatment difference was not statistically significant ( 37 ml ; 95% ci , 88 to 15 ml ; p = .162 ) ( fig 2 ) . there were no differences in key secondary end points , including the change from baseline in individual serial fev1 assessments over time at week 24 .
these showed sustained 24-h duration of action for both once - daily ff / vi and bid fp / sal at all time points ( fig 3 ) .
the adjusted mean treatment differences between ff / vi and fp / sal ranged from 2 to 58 ml . no important differences were seen between ff / vi vs fp / sal for the secondary end points of time to onset of bronchodilator effect , 0- to 4-h serial wmfev1 postdose at randomization and at week 24 , percentage of patients obtaining a  12% and  200-ml increase from baseline in fev1 at 12 and 24 h at week 24 , and change from baseline in clinic visit trough ( prebronchodilator and predose ) fev1 at week 24 ( table 2 ) .
change from baseline in predose fev1 over the 24-week treatment period is shown in e - figure 1 .
adjusted means for 0- to 24-h serial weighted mean fev1 at week 24 ( intention - to - treat population ) .
see figure 1 legend for expansion of other abbreviations . adjusted mean change from baseline in fev1 over time at week 24 for ff / vi dosed od in the evening and fp / sal dosed bd ( intention - to - treat population ) .
secondary end points data are presented as least squares mean  se change from baseline unless otherwise indicated .
intention - to - treat population , n = 403 ( ff / vi 100/25 g od pm ) and n = 403 ( fp / sal 250 g bid ) .
hr = hazard ratio ; wm = weighted mean . see table 1 legend for expansion of other abbreviations .
results are for all secondary end points other than the end point individual serial fev1 assessments at week 24 ( see fig 3 ) .
improvements from baseline in the aqlq+12 , asthma control test , and eq-5d asthma health outcomes assessments were observed for both ff / vi and fp / sal .
health outcomes assessments intention - to - treat population , n = 403 ( ff / vi 100/25 g od pm ) and n = 403 ( fp / sal 250 g bid ) .
act = asthma control test ; aqlq+12 = asthma quality of life + 12 questionnaire ; eq-5d = european quality of life-5 dimensions ; n / a = not applicable ; vas = visual analog scale .
aqlq+12 , act , and eq-5d vas score , analysis of covariance was used , with covariates of baseline score , country , sex , age , and treatment ; eq-5d , logistic regression analysis was used , with covariates of baseline , region , sex , age , and treatment .
the overall incidence of aes and saes reported while on treatment are presented in table 4 .
the most frequently occurring aes reported by both groups were nasopharyngitis and headache ; treatment - related aes were similar between groups ( table 4 ) .
nine patients reported on - treatment saes ( four receiving ff / vi and five receiving fp / sal ) ( table 4 ) .
saes were single events with the exception of asthma exacerbation and pneumonia ( one pretreatment and one on treatment [ fp / sal ] ) .
on - treatment aes  3% in any treatment group , all saes , and treatment - related aes ( intention - to - treat population ) data are presented as no .
ae = adverse event ; sae = serious adverse event ; urti = upper respiratory tract infection .
there was no statistically significant difference between ff / vi and fp / sal in 24-h uc excretion at week 24 ( adjusted treatment ratio , 0.85 ; 95% ci , 0.72 - 1.02 ; p = .075 ) ( fig 4 ) .
however , 24-h uc excretion did increase in both groups from baseline to week 24 ( ratio to baseline , 1.11 and 1.21 for ff / vi and fp / sal , respectively )
. adjusted ratios to baseline for 24-h urinary cortisol excretion at week 24 ( urinary cortisol population ) .
the incidence of asthma exacerbations was low , and there was no difference between groups ( 3% vs 2% on fp / sal vs ff / vi , respectively [ on - treatment events ] ) .
eight ( 2% ) patients in the ff / vi group and seven ( 2% ) in the fp / sal group withdrew because of their exacerbation .
one patient in the ff / vi group and two in the fp / sal group were hospitalized because of their exacerbations .
no clinically relevant treatment effects on vital signs ( e - appendix 5 ) or liver function parameters were found , with the exception of one patient in the fp / sal group who met liver stopping criteria of alanine aminotransferase levels more than eight times the upper limit of normal , which was reported as an ae but was not considered treatment related .
most patients ( 89% ) in both treatment groups completed the 24-week treatment period ( fig 1 ) .
ae = adverse event ; bd = twice daily ; ff = fluticasone furoate ; fp = fluticasone propionate ; itt = intention to treat ; od = once daily ; sal = salmeterol ; vi = vilanterol .
main reason was that patients did not meet inclusion / exclusion criteria ( n = 613 [ 39% ] ) .
main reason was that patients did not meet continuation criteria ( n = 103 [ 7% ] ) .
patient demographics and baseline lung function ( intention - to - treat population ) data are presented as mean  sd or no .
ff = fluticasone furoate ; fp = fluticasone propionate ; ics = inhaled corticosteroid ; laba = long - acting 2-agonist ; od = once daily ; sal = salmeterol ; vi = vilanterol .
patients needed to have been maintained on a medium dose of ics ( eg , fp 250 g bid ) for  4 wk before screening .
improvements from baseline in 0- to 24-h serial wmfev1 were seen with both ff / vi ( 341 ml ) and fp / sal ( 377 ml ) ; however , the adjusted mean treatment difference was not statistically significant ( 37 ml ; 95% ci , 88 to 15 ml ; p = .162 ) ( fig 2 ) .
there were no differences in key secondary end points , including the change from baseline in individual serial fev1 assessments over time at week 24 .
these showed sustained 24-h duration of action for both once - daily ff / vi and bid fp / sal at all time points ( fig 3 ) .
the adjusted mean treatment differences between ff / vi and fp / sal ranged from 2 to 58 ml . no important differences were seen between ff / vi vs fp / sal for the secondary end points of time to onset of bronchodilator effect , 0- to 4-h serial wmfev1 postdose at randomization and at week 24 , percentage of patients obtaining a  12% and  200-ml increase from baseline in fev1 at 12 and 24 h at week 24 , and change from baseline in clinic visit trough ( prebronchodilator and predose ) fev1 at week 24 ( table 2 ) .
change from baseline in predose fev1 over the 24-week treatment period is shown in e - figure 1 .
adjusted means for 0- to 24-h serial weighted mean fev1 at week 24 ( intention - to - treat population ) .
see figure 1 legend for expansion of other abbreviations . adjusted mean change from baseline in fev1 over time at week 24 for ff / vi dosed od in the evening and fp / sal dosed bd ( intention - to - treat population ) .
secondary end points data are presented as least squares mean  se change from baseline unless otherwise indicated .
n = 403 ( ff / vi 100/25 g od pm ) and n = 403 ( fp / sal 250 g bid ) .
hr = hazard ratio ; wm = weighted mean . see table 1 legend for expansion of other abbreviations .
results are for all secondary end points other than the end point individual serial fev1 assessments at week 24 ( see fig 3 ) .
improvements from baseline in 0- to 24-h serial wmfev1 were seen with both ff / vi ( 341 ml ) and fp / sal ( 377 ml ) ; however , the adjusted mean treatment difference was not statistically significant ( 37 ml ; 95% ci , 88 to 15 ml ; p = .162 ) ( fig 2 ) .
there were no differences in key secondary end points , including the change from baseline in individual serial fev1 assessments over time at week 24 .
these showed sustained 24-h duration of action for both once - daily ff / vi and bid fp / sal at all time points ( fig 3 ) .
the adjusted mean treatment differences between ff / vi and fp / sal ranged from 2 to 58 ml . no important differences were seen between ff / vi vs fp / sal for the secondary end points of time to onset of bronchodilator effect , 0- to 4-h serial wmfev1 postdose at randomization and at week 24 , percentage of patients obtaining a  12% and  200-ml increase from baseline in fev1 at 12 and 24 h at week 24 , and change from baseline in clinic visit trough ( prebronchodilator and predose ) fev1 at week 24 ( table 2 ) .
change from baseline in predose fev1 over the 24-week treatment period is shown in e - figure 1 .
adjusted means for 0- to 24-h serial weighted mean fev1 at week 24 ( intention - to - treat population ) .
see figure 1 legend for expansion of other abbreviations . adjusted mean change from baseline in fev1 over time at week 24 for ff / vi dosed od in the evening and fp / sal dosed bd ( intention - to - treat population ) .
secondary end points data are presented as least squares mean  se change from baseline unless otherwise indicated .
n = 403 ( ff / vi 100/25 g od pm ) and n = 403 ( fp / sal 250 g bid ) .
hr = hazard ratio ; wm = weighted mean . see table 1 legend for expansion of other abbreviations .
results are for all secondary end points other than the end point individual serial fev1 assessments at week 24 ( see fig 3 ) .
improvements from baseline in the aqlq+12 , asthma control test , and eq-5d asthma health outcomes assessments were observed for both ff / vi and fp / sal .
health outcomes assessments intention - to - treat population , n = 403 ( ff / vi 100/25 g od pm ) and n = 403 ( fp / sal 250 g bid ) .
act = asthma control test ; aqlq+12 = asthma quality of life + 12 questionnaire ; eq-5d = european quality of life-5 dimensions ; n / a = not applicable ; vas = visual analog scale . see table 1 legend for expansion of other abbreviations .
aqlq+12 , act , and eq-5d vas score , analysis of covariance was used , with covariates of baseline score , country , sex , age , and treatment ; eq-5d , logistic regression analysis was used , with covariates of baseline , region , sex , age , and treatment .
the overall incidence of aes and saes reported while on treatment are presented in table 4 .
the most frequently occurring aes reported by both groups were nasopharyngitis and headache ; treatment - related aes were similar between groups ( table 4 ) .
nine patients reported on - treatment saes ( four receiving ff / vi and five receiving fp / sal ) ( table 4 ) .
saes were single events with the exception of asthma exacerbation and pneumonia ( one pretreatment and one on treatment [ fp / sal ] ) .
on - treatment aes  3% in any treatment group , all saes , and treatment - related aes ( intention - to - treat population ) data are presented as no . ( % ) . ae = adverse event ; sae = serious adverse event ; urti = upper respiratory tract infection .
see table 1 legend for expansion of other abbreviations . there was no statistically significant difference between ff / vi and fp / sal in 24-h uc excretion at week 24 ( adjusted treatment ratio , 0.85 ; 95% ci , 0.72 - 1.02 ; p = .075 ) ( fig 4 ) .
however , 24-h uc excretion did increase in both groups from baseline to week 24 ( ratio to baseline , 1.11 and 1.21 for ff / vi and fp / sal , respectively ) . adjusted ratios to baseline for 24-h urinary cortisol excretion at week 24 ( urinary cortisol population ) . see figure 1 and 2 legends for expansion of abbreviations .
the incidence of asthma exacerbations was low , and there was no difference between groups ( 3% vs 2% on fp / sal vs ff / vi , respectively [ on - treatment events ] ) .
eight ( 2% ) patients in the ff / vi group and seven ( 2% ) in the fp / sal group withdrew because of their exacerbation .
one patient in the ff / vi group and two in the fp / sal group were hospitalized because of their exacerbations .
no clinically relevant treatment effects on vital signs ( e - appendix 5 ) or liver function parameters were found , with the exception of one patient in the fp / sal group who met liver stopping criteria of alanine aminotransferase levels more than eight times the upper limit of normal , which was reported as an ae but was not considered treatment related .
in this study of patients aged  12 years with persistent asthma uncontrolled on a medium dose of ics , ff / vi 100/25 g once daily in the evening was not significantly different from fp / sal 250/50 g bid for the primary end point of 0- to 24-h serial wmfev1 at week 24 or for any of the secondary end points .
the ae profiles for both treatments were similar , and those aes reported with fp / sal were consistent with those previously reported with this drug combination .
according to current asthma guidelines , these patients would require a step up in their asthma treatment from step 3 to 4 .
lack of asthma control in the patient population at baseline was evident by an fev1 of approximately 68% of the predicted normal value for both groups and by the fact that  50% of patients had an asthma control test score of < 20 .
a number of studies have shown that nonadherence to asthma therapy is an important reason for loss of asthma control in some patients .
adherence to the treatment schedule was high during the study ( > 94% in both groups ) , although the artificial setting of a clinical trial may have encouraged normally nonadherers to take their medication .
if poor adherence to the dosing schedule is an important factor in loss of asthma control , then once - daily dosing ( as opposed to bid dosing ) such as that provided by ff / vi may represent a more - convenient treatment option for patients in a real - world setting .
no differences in asthma control test scores or in measures of quality of life ( aqlq+12 and eq-5d ) were shown in the present study .
a difference of 1.4 was observed between groups on the eq-5d test , but this difference was not statistically significant .
the outcomes of the post hoc analysis ( e - appendix 3 ) suggest that ff / vi may provide clinically relevant improvements in certain patient - reported quality - of - life measures ( environmental domain of the aqlq+12 in the present study ) , as well as in the percentage of patients who improved by at least the minimally important difference of 0.5 , that were not reported with fp / sal .
however , this statement is speculative and requires further evaluation in real - world studies outside the environment of a clinical trial .
ff / vi and fp / sal were well tolerated , and ff / vi had a similar ae profile to fp / sal . the ae profile with ff / vi reported in the present study is consistent with that seen in the two ff dose - ranging studies that included the 100 g once - daily dose and the two studies of vi 25 g plus concurrent ics .
most of the saes reported in the present study were single events , and none were considered treatment related .
asthma exacerbations requiring hospitalization occurred in one patient receiving ff / vi and two patients receiving fp / sal . a potential effect of ics treatment
is reduction in uc levels as a result of suppression of the hypothalamic - pituitary - adrenal axis , although this usually only occurs at higher doses of ics . in earlier phase dose - ranging studies , once - daily ff 100 or 200 g did not significantly inhibit 24-h uc levels relative to placebo . in the current study , clinically insignificant increases in uc levels from baseline were reported , and no statistically significant differences were observed between the groups at week 24 .
labas have occasional side effects , such as headache , tremor , and hypertension . in the present study ,
no clinically relevant effects of ff / vi or fp / sal were found in measures of bp or pulse rate . it may be considered a limitation that the study duration was too short to reliably collect information on important end points such as exacerbations . also , while a once - daily dosing schedule could provide greater convenience to the patient and may therefore increase compliance to treatment , the double - blind , double - dummy nature of the study , together with the very high compliance levels during the study , means that the full benefit of once - daily dosing compared with bid dosing could not be realized in this study .
this can only be investigated in a real - world effectiveness study , such as the salford lung study , which is now under way .
it is possible that prestudy ics adherence was lower than anticipated by the protocol , as suggested by the high degree of fev1 reversibility seen at screening .
once - daily ff / vi had similar treatment effects to bid fp / sal in improving lung function and health status in this double - blind randomized study .
it remains to be seen whether it will be superior in a real - world setting . in conclusion , there was no difference in efficacy or safety between ff / vi 100/25 g administered once daily in the evening and fp / sal 250/50 g administered bid .
 background : the combination of fluticasone furoate ( ff ) , a novel inhaled corticosteroid ( ics ) , and vilanterol ( vi ) , a long - acting 2 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 g , n = 403 ) once daily in the evening delivered through ellipta ( glaxosmithkline ) dry powder inhaler , or fp / sal ( 250/50 g , 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 
Trial registry:
Materials and Methods
Patients
Study Design and Treatments
Outcome Measurements
Safety Evaluations
Statistical Analysis
Results
Study Population
Efficacy Assessments
Lung Function:
Health Outcomes
Safety Assessments
Discussion
Supplementary Material