VEG111485: A QTc Study of Pazopanib

This is a Phase I, randomized, double-blind, placebo-controlled, parallel group study designed to estimate the effects of repeated, once daily oral dosing of pazopanib on electrocardiographic parameters with a particular focus on its effect on cardiac repolarization (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, a drug known to cause mild QTc interval prolongation, is included as a positive control to validate the ability of the study to detect a small prolongation in the QTc interval. Digital 12-lead electrocardiograms (ECGs) will be extracted from continuous ECG recordings obtained via a Holter monitor. The effects of pazopanib and moxifloxacin on cardiac repolarization will be compared with placebo. This study will also assess the pharmacokinetic-pharmacodynamic relationship between plasma concentrations of pazopanib and its metabolites and their effects, if any, on cardiac repolarization, specifically on the QT interval.