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A repeat‐dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects
Author(s) -
Kempsford Rodger,
Allen Ann,
Kelly Kathryn,
Saggu Parminder,
Crim Courtney
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12243
Subject(s) - moxifloxacin , placebo , medicine , crossover study , confidence interval , fluticasone propionate , randomized controlled trial , dosing , anesthesia , corticosteroid , antibiotics , chemistry , biochemistry , alternative medicine , pathology
Aims 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. Methods 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 μg) 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 μg), oral moxifloxacin (400 mg) or placebo. Results There was a lack of effect of FF / VI (200/25 μg) on QT c F (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 μg, 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% CI s <10 ms (0–24 h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QT ci, with time‐matched mean differences from baseline relative to placebo of >10 ms (1–8 h postdose). Conclusions Repeat once‐daily dosing of FF / VI (200/25 μg), 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 μg) demonstrated a small transient effect on QTcF but not on QT ci.