A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects.

ABSTRACT: This study was designed as a thorough QT (TQT) study to evaluate the effects of fluticasone furoate (FF)/vilanterol (VI) in healthy subjects. Supportive data from a TQT study conducted with FF are also presented.This was a randomized, placebo- and positive-controlled, double-dummy, double-blind, four-way crossover study, in which healthy subjects (n = 85) were randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100??g) or placebo or single-dose oral moxifloxacin (single-blind, 400?mg). In the supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF (4000??g), oral moxifloxacin (400?mg) or placebo.There was a lack of effect of FF/VI (200/25??g) on QTcF (Fridericia's correction); all time-matched mean differences from baseline relative to placebo (0-24?h) were <5 ms, with upper 90% confidence intervals (CI) of <10 ms. At 800/100??g, FF/VI had no significant clinical effect on QTcF except at 30?min postdose when the 90% CI was >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually corrected) was observed at either strength of FF/VI, with mean time-matched treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0-24?h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time-matched mean differences from baseline relative to placebo of >10 ms (1-8?h postdose).Repeat once-daily dosing of FF/VI (200/25??g), which is the highest therapeutic strength used in phase?III studies, is not associated with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI (800/100??g) demonstrated a small transient effect on QTcF but not on QTci.

SUBMITTER: Kempsford R 

PROVIDER: S-EPMC3952721 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature