title: Pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol as a triple therapy in healthy volunteers.
abstract: OBJECTIVE
  Two single-center, four-way, single-dose, crossover studies assessed the systemic exposure, systemic pharmacodynamics (PD), and safety profile of the closed triple fluticasone furoate/ umeclidinium/vilanterol (FF/UMEC/VI) therapy compared with dual therapies. These are the first studies where pharmacokinetic (PK) profile assessment was possible for this inhaled triple fixed-dose combination product.
  
  
  METHODS
  Healthy volunteers were randomized to receive 4 consecutive inhalations (each administered as a single dose) via a single ELLIPT® dry powder inhaler: in study 1 (CTT116415/NCT01691547), FF/UMEC/VI at total doses of 400/500/100 μg, FF/UMEC 400/500 μg, UMEC/VI 500/100 μg, or FF/VI 400/100 μg; in study 2 (200587/NCT01894386), FF/UMEC/VI at total doses of 400/500/100 μg or 400/250/100 μg, FF/VI 400/100 μg, or UMEC/VI 250/100 μg. PK and PD parameters and safety were assessed.
  
  
  RESULTS
  Of 88 subjects, 95% completed both studies and received all planned treatments. Total systemic exposure was similar for FF, UMEC, and VI when administered as a triple therapy compared with FF/VI and UMEC/VI. No clinically significant systemic PD findings were detected. The incidence of adverse events was low and similar across treatment arms.
  
  
  CONCLUSIONS
  Systemic exposure to all three components of the closed triple therapy, following single-dose delivery, was similar to that seen with the dual therapies FF/VI and UMEC/VI. The delivered lung dose and safety profile of all three agents, delivered via a single inhaler, are expected to be similar to those of the dual therapies.
authors.forename: Noushin
authors.initials: N
authors.lastname: Brealey
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Gupta
authors.forename: Jessica
authors.initials: J
authors.lastname: Renaux
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mehta
authors.forename: Ann
authors.initials: A
authors.lastname: Allen
authors.forename: Alex
authors.initials: A
authors.lastname: Henderson
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D011812:Quinuclidines; C550468:vilanterol; C523187:fluticasone furoate