No Evidence of QT Prolongation With Supratherapeutic Doses of Aleglitazar

Abstract

Aleglitazar is a dual peroxisome proliferator-activated receptor (PPAR)-α/γ agonist in clinical development, designed to offer a balanced activation of PPAR-α and PPAR-γ. A phase 2 trial has demonstrated improvements in dyslipidemia and glycemic control and reduction of cardiovascular risk markers in patients with type 2 diabetes mellitus treated with aleglitazar. This study evaluated whether supratherapeutic doses of aleglitazar affect cardiac repolarization, as detected by changes in the QT interval.Healthy subjects were randomized to receive single oral doses of placebo, 300 μg aleglitazar, 3000 μg aleglitazar, and 400 mg moxifloxacin, in 1 of 4 sequences. Triplicate 12-lead electrocardiogram measurements were recorded predose and regularly (0.75-72 hours) after each treatment. The primary outcome was measurement of QT interval using a study-specific correction factor for heart rate.Administration of aleglitazar (300 μg and 3000 μg) did not cause any significant QT prolongation and after aleglitazar treatment any mean increases from placebo were <5 msec, at all time points. There was a trend for aleglitazar to cause a small dose-dependent decrease in QT interval using a study-specific correction factor for heart rate. The incidence of adverse events was similar with aleglitazar (18%-20%) and placebo (26%).Single supratherapeutic doses of aleglitazar are not associated with prolongation of the QT interval corrected for heart rate.