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 ?g, FF/UMEC 400/500 ?g, UMEC/VI 500/100 ?g, or FF/VI 400/100 ?g; in study 2 (200587/NCT01894386), FF/UMEC/VI at total doses of 400/500/100 ?g or 400/250/100 ?g, FF/VI 400/100 ?g, or UMEC/VI 250/100 ?g. 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.

SUBMITTER: Brealey N 

PROVIDER: S-EPMC4531525 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature