Mark T Dransfield1, Gregory Feldman2, Phillip Korenblat3, Craig F LaForce4, Nicholas Locantore5, Massimo Pistolesi6, Michael L Watkins5, Courtney Crim5, Fernando J Martinez7. 1. UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham VA Medical Center, Birmingham, AL 35233, USA. Electronic address: mdrans99@uab.edu. 2. S. Carolina Pharmaceutical Research, Spartanburg, SC 29303, USA. 3. Clinical Research Center LLB, St Louis, MO 63141, USA. 4. North Carolina Clinical Research, Raleigh, NC 27607, USA. 5. GlaxoSmithKline, Research Triangle Park, NC 27709, USA. 6. University of Florence, Florence, 50121 Firenze, Italy. 7. University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
BACKGROUND:Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL). METHODS: Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged ≥40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weightedmean FEV(1) (wmFEV(1)) on Day 84. Safety was also assessed. RESULTS: In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEV(1) was significantly greater with FF/VI than FP/SAL (Δ80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0-24 h wmFEV(1) was not significantly greater with FF/VI than FP/SAL (Δ29 mL, P = 0.267; Δ25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Δ41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments. CONCLUSIONS: Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974.
RCT Entities:
BACKGROUND:Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL). METHODS: Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged ≥40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weighted mean FEV(1) (wmFEV(1)) on Day 84. Safety was also assessed. RESULTS: In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEV(1) was significantly greater with FF/VI than FP/SAL (Δ80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0-24 h wmFEV(1) was not significantly greater with FF/VI than FP/SAL (Δ29 mL, P = 0.267; Δ25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Δ41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments. CONCLUSIONS: Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974.
Authors: Gillian Stynes; Henrik Svedsater; Jaro Wex; Sally Lettis; David Leather; Emanuela Castelnuovo; Michelle Detry; Scott Berry Journal: Respir Res Date: 2015-02-15
Authors: Xia Chen; Xin Zheng; Ji Jiang; Pei Hu; Kai Wu; Lihong Zhuang; Lian Liu; Xin Du; Rodger Kempsford; Ann Allen Journal: Pharmacotherapy Date: 2015-06-09 Impact factor: 4.705