title: Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial.
abstract: Background Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting β(2) agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma.  Trial design A multicentre, randomised, double-blind, parallel-group, placebo-controlled study.  Methods Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0-4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV(1)) (23-24 h postdose; day 29) and wm FEV(1) (0-4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment.  Results 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV(1) per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0-4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI -3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV(1) (mean difference 183 ml) and 0-4 h postdose wm FEV(1) (mean difference 236 ml).  Conclusion FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.  Trial registration number clinical trials.gov-NCT00731822.
authors.affiliation: Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
authors.forename: P S
authors.initials: PS
authors.lastname: Bakke
authors.forename: L
authors.initials: L
authors.lastname: Bjermer
authors.forename: S
authors.initials: S
authors.lastname: Steinshamn
authors.forename: C
authors.initials: C
authors.lastname: Scott-Wilson
authors.forename: C
authors.initials: C
authors.lastname: Crim
authors.forename: L
authors.initials: L
authors.lastname: Sanford
authors.forename: B
authors.initials: B
authors.lastname: Haumann