Thorough QT study of the effects of vildagliptin, a dipeptidyl peptidase IV inhibitor, on cardiac repolarization and conduction in healthy volunteers

作者：Y.-L. He, Y. Zhang, Denise Serra, Y. Wang, Monica Ligueros‐Saylan, William P. Dole · 发表于：Current Medical Research and Opinion · 年份：2011 · DOI：10.1185/03007995.2011.585395 · 被引用次数：16 · 研究领域：Cardiac electrophysiology and arrhythmias、Diabetes Treatment and Management、Heart Failure Treatment and Management

OBJECTIVE: This randomized, double-blind study evaluated the effects of vildagliptin, a dipeptidyl peptidase IV inhibitor for treating type 2 diabetes, on cardiac repolarization and conduction. METHODS: Healthy volunteers (n = 101) were randomized (1:1:1:1 ratio) to vildagliptin 100 or 400 mg, moxifloxacin 400 mg (active control), or placebo once daily for 5 days. Electrocardiograms were recorded at baseline and day 5 for 24 hours post-dose. Placebo-adjusted mean change from baseline in QT interval, heart-rate-corrected QT intervals by Fridericia's (QTcF) or Bazett's (QTcB) formula, and PR and QRS intervals were compared at each time-point (time-matched analysis) and for values averaged across the dosing period (time-averaged analysis). RESULTS: For time-matched analysis, mean changes in QTcF with vildagliptin were below predefined limits for QTc prolongation (mean increase <5 ms; upper 90% confidence interval [CI] < 10 ms), except for vildagliptin 100 mg at 1 and 8 hours post-dose (upper 90% CI > 10 ms). With moxifloxacin, significant QTcF prolongation occurred at most time-points, demonstrating assay sensitivity. No vildagliptin- or placebo-treated volunteer had QTcF > 450 ms. Incidences of QTcF increases ≥30 ms with vildagliptin (100 and 400 mg) and placebo were similar (4-8%) and were much lower than with moxifloxacin (39%). No QTcF increase ≥60 ms was observed with vildagliptin or placebo (versus one with moxifloxacin). Time-averaged, time-matched, and categorical analys...