BACKGROUND:Fluticasone furoate (FF) is an inhaled corticosteroid (ICS) with 24-hour activity in development as a once-daily treatment for the long-term management of asthma. OBJECTIVE: To assess the efficacy and safety of 4 doses of once-daily FF administered using a dry powder inhaler in patients (≥12 years) with moderate asthma, uncontrolled on low-dose ICS (fluticasone propionate [FP] 200 μg/day or equivalent). METHODS: This double-blind, placebo-controlled, dose-ranging study randomized 622 patients to 1 of 6 treatments: FF (100, 200, 300, or 400 μg) once daily in the evening, FP 250 μg twice daily (active control), or placebo for 8 weeks. The primary endpoint was the change from baseline in predose evening forced expiratory colume in 1 second (FEV1) at week 8. RESULTS: At week 8, relative to placebo, all doses of FF once daily and FP twice daily demonstrated significantly (P < .001) greater increases from baseline and greater than 200-mL increases in predose FEV1. There was no evidence of a dose-response relationship between FF doses. Improvement with once-daily FF was similar to or greater than that for twice-daily FP. Secondary efficacy endpoint findings generally supported the efficacy of FF 100 to 400 μg once daily, although statistically significant improvements versus placebo in symptom-free 24-hour periods were only reported for FF 400 μg. There were few withdrawals due to lack of efficacy. Oral candidiasis was reported in 0 to 4% of patients; 24-hour urinary cortisol excretion ratios were similar across active treatment groups and not significantly different from placebo. CONCLUSION:FF 100 to 400 μg once daily in the evening is effective and well tolerated in patients with asthma uncontrolled on low-dose ICS, with 100 μg and 200 μg, considered the most applicable doses in this asthma population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603278.
RCT Entities:
BACKGROUND:Fluticasone furoate (FF) is an inhaled corticosteroid (ICS) with 24-hour activity in development as a once-daily treatment for the long-term management of asthma. OBJECTIVE: To assess the efficacy and safety of 4 doses of once-daily FF administered using a dry powder inhaler in patients (≥12 years) with moderate asthma, uncontrolled on low-dose ICS (fluticasone propionate [FP] 200 μg/day or equivalent). METHODS: This double-blind, placebo-controlled, dose-ranging study randomized 622 patients to 1 of 6 treatments: FF (100, 200, 300, or 400 μg) once daily in the evening, FP 250 μg twice daily (active control), or placebo for 8 weeks. The primary endpoint was the change from baseline in predose evening forced expiratory colume in 1 second (FEV1) at week 8. RESULTS: At week 8, relative to placebo, all doses of FF once daily and FP twice daily demonstrated significantly (P < .001) greater increases from baseline and greater than 200-mL increases in predose FEV1. There was no evidence of a dose-response relationship between FF doses. Improvement with once-daily FF was similar to or greater than that for twice-daily FP. Secondary efficacy endpoint findings generally supported the efficacy of FF 100 to 400 μg once daily, although statistically significant improvements versus placebo in symptom-free 24-hour periods were only reported for FF 400 μg. There were few withdrawals due to lack of efficacy. Oral candidiasis was reported in 0 to 4% of patients; 24-hour urinary cortisol excretion ratios were similar across active treatment groups and not significantly different from placebo. CONCLUSION:FF 100 to 400 μg once daily in the evening is effective and well tolerated in patients with asthma uncontrolled on low-dose ICS, with 100 μg and 200 μg, considered the most applicable doses in this asthma population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603278.
Authors: Amanda Oliver; Sandi VanBuren; Ann Allen; Melanie Hamilton; Lee Tombs; Rodger Kempsford; Paul Qaqundah Journal: Clin Pharmacol Drug Dev Date: 2014-02-06
Authors: Ekkehard Werner Zöllner; Carl J Lombard; Ushma Galal; Stephen Hough; Elvis M Irusen; Eugene Weinberg Journal: BMJ Open Date: 2013-08-01 Impact factor: 2.692
Authors: Jan Lötvall; Eric D Bateman; William W Busse; Paul M O'Byrne; Ashley Woodcock; William T Toler; Loretta Jacques; Caroline Goldfrad; Eugene R Bleecker Journal: J Negat Results Biomed Date: 2014-06-13
Authors: Annette S Gross; Caroline Goldfrad; Soichiro Hozawa; Mark H James; Christine S Clifton; Yutaro Sugiyama; Loretta Jacques Journal: BMC Pulm Med Date: 2015-12-24 Impact factor: 3.317
Authors: Paul M O'Byrne; Eugene R Bleecker; Eric D Bateman; William W Busse; Ashley Woodcock; Richard Forth; William T Toler; Loretta Jacques; Jan Lötvall Journal: Eur Respir J Date: 2013-10-17 Impact factor: 16.671
Authors: Ashley Woodcock; Eugene R Bleecker; Jan Lötvall; Paul M O'Byrne; Eric D Bateman; Hilary Medley; Anna Ellsworth; Loretta Jacques; William W Busse Journal: Chest Date: 2013-10 Impact factor: 9.410
Authors: Ashley Woodcock; Jan Lötvall; William W Busse; Eric D Bateman; Sally Stone; Anna Ellsworth; Loretta Jacques Journal: BMC Pulm Med Date: 2014-07-09 Impact factor: 3.317