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Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial.

O'Byrne PM, Woodcock A, Bleecker ER, Bateman ED, Lötvall J, Forth R, Medley H, Jacques L, Busse WW - Respir. Res. (2014)

Bottom Line: 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%).

View Article: PubMed Central - PubMed

Affiliation: Michael G DeGroote School of Medicine, Hamilton, ON, Canada. obyrnep@mcmaster.ca.

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.

Results: There 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%).

Conclusion: FF 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.

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Related in: MedlinePlus

Adjusted treatment differences for the change from baseline for primary, and selected secondary and other endpoints (intent-to-treat population). *Data were analysed using a closed step-down statistical hierarchy, whereby failure to achieve significance at any point in the hierarchy meant that statistical significance could not be inferred for subsequent endpoints in the hierarchy. Solid lines indicate a significant treatment difference; dashed lines indicate differences which are not significant (evening PEF) or for which significance cannot be inferred (all remaining endpoints); FEV1 = forced expiratory volume in one second; PEF = peak expiratory flow; ACT = Asthma Control Test; AQLQ = Asthma Quality of Life Questionnaire; CI = confidence interval.
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Fig2: Adjusted treatment differences for the change from baseline for primary, and selected secondary and other endpoints (intent-to-treat population). *Data were analysed using a closed step-down statistical hierarchy, whereby failure to achieve significance at any point in the hierarchy meant that statistical significance could not be inferred for subsequent endpoints in the hierarchy. Solid lines indicate a significant treatment difference; dashed lines indicate differences which are not significant (evening PEF) or for which significance cannot be inferred (all remaining endpoints); FEV1 = forced expiratory volume in one second; PEF = peak expiratory flow; ACT = Asthma Control Test; AQLQ = Asthma Quality of Life Questionnaire; CI = confidence interval.

Mentions: For the primary endpoint, the change from baseline evening trough FEV1 at Week 12 was 157 mL with FF 50 mcg and 38 mL with placebo; the treatment difference of 120 mL (p = 0.012) was statistically significant (Table 2; Figure 2). Repeated measures analysis demonstrated that trough FEV1 was consistently greater with FF 50 mcg vs. placebo throughout the study period (Figure 3). Supporting analysis of the per protocol population was similar (treatment difference in favor of FF 50 mcg: 131 mL [95% CI: 38, 224]; p = 0.006).Table 2


Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial.

O'Byrne PM, Woodcock A, Bleecker ER, Bateman ED, Lötvall J, Forth R, Medley H, Jacques L, Busse WW - Respir. Res. (2014)

Adjusted treatment differences for the change from baseline for primary, and selected secondary and other endpoints (intent-to-treat population). *Data were analysed using a closed step-down statistical hierarchy, whereby failure to achieve significance at any point in the hierarchy meant that statistical significance could not be inferred for subsequent endpoints in the hierarchy. Solid lines indicate a significant treatment difference; dashed lines indicate differences which are not significant (evening PEF) or for which significance cannot be inferred (all remaining endpoints); FEV1 = forced expiratory volume in one second; PEF = peak expiratory flow; ACT = Asthma Control Test; AQLQ = Asthma Quality of Life Questionnaire; CI = confidence interval.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256920&req=5

Fig2: Adjusted treatment differences for the change from baseline for primary, and selected secondary and other endpoints (intent-to-treat population). *Data were analysed using a closed step-down statistical hierarchy, whereby failure to achieve significance at any point in the hierarchy meant that statistical significance could not be inferred for subsequent endpoints in the hierarchy. Solid lines indicate a significant treatment difference; dashed lines indicate differences which are not significant (evening PEF) or for which significance cannot be inferred (all remaining endpoints); FEV1 = forced expiratory volume in one second; PEF = peak expiratory flow; ACT = Asthma Control Test; AQLQ = Asthma Quality of Life Questionnaire; CI = confidence interval.
Mentions: For the primary endpoint, the change from baseline evening trough FEV1 at Week 12 was 157 mL with FF 50 mcg and 38 mL with placebo; the treatment difference of 120 mL (p = 0.012) was statistically significant (Table 2; Figure 2). Repeated measures analysis demonstrated that trough FEV1 was consistently greater with FF 50 mcg vs. placebo throughout the study period (Figure 3). Supporting analysis of the per protocol population was similar (treatment difference in favor of FF 50 mcg: 131 mL [95% CI: 38, 224]; p = 0.006).Table 2

Bottom Line: 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%).

View Article: PubMed Central - PubMed

Affiliation: Michael G DeGroote School of Medicine, Hamilton, ON, Canada. obyrnep@mcmaster.ca.

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.

Results: There 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%).

Conclusion: FF 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.

Show MeSH
Related in: MedlinePlus