title: Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients.
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 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.
  
  
  BACKGROUND
  clinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974.
authors.affiliation: 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.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: S. Carolina Pharmaceutical Research, Spartanburg, SC 29303, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Feldman
authors.affiliation: Clinical Research Center LLB, St Louis, MO 63141, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Korenblat
authors.affiliation: North Carolina Clinical Research, Raleigh, NC 27607, USA.
authors.forename: Craig F
authors.initials: CF
authors.lastname: LaForce
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Locantore
authors.affiliation: University of Florence, Florence, 50121 Firenze, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pistolesi
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Watkins
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.affiliation: University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; C550468:vilanterol; C523187:fluticasone furoate; D000420:Albuterol
keywords: Chronic obstructive pulmonary disease; Head-to-head; Inhaled corticosteroid; Long-acting β(2)-agonist; Lung function