A repeat‐dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects. (March 2014)

• Record Type: Journal Article
• Authors: Kempsford, Rodger; Allen, Ann; Kelly, Kathryn; Saggu, Parminder; Crim, Courtney
• Is Part Of: British journal of clinical pharmacology. Volume 77:Number 3(2014:Mar.)
• Page Start: 466
• Page End: 479
• Publication Date: 2014-03
• Subjects: Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.12243
• Languages: English
• ISSNs: 0306-5251

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bcp12243-sec-0003" sec-type="section"> <title>Aims</title> <p>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.</p> </sec> <sec id="bcp12243-sec-0004" sec-type="section"> <title>Methods</title> <p>This was a randomized, placebo‐ and positive‐controlled, double‐dummy, double‐blind, four‐way crossover study, in which healthy subjects (<italic>n</italic> = 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 (<italic>n</italic> = 40) were randomized to single‐dose inhaled FF (4000 μg), oral moxifloxacin (400 mg) or placebo.</p> </sec> <sec id="bcp12243-sec-0005" sec-type="section"> <title>Results</title> <p>There was a lack of effect of FF/VI (200/25 μg) 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 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% 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).</p> </sec> <sec id="bcp12243-sec-0006" sec-type="section"> <title>Conclusions</title> <p>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 QTci.</p> </sec> </abstract>