| Popis: |
This double-blind, randomized, placebo- and active-controlled, parallel group trial evaluated the potential for multiple-dose fasiglifam to prolong the QT/QTc interval in healthy adults. A total of 280 men and women aged 18-50 years were randomized to receive 14 days of fasiglifam 50 mg (n = 69), fasiglifam 400 mg (n = 70), or placebo (n = 70), or 13 days of placebo followed by single-dose moxifloxacin 400 mg (positive control; n = 71). The primary endpoint was the least square mean difference between fasiglifam and placebo in time-matched change from baseline to last dosing day in QT interval corrected using the Fridericia method (QTcF, calculated as QT/RR(0) (.333) ). For both fasiglifam doses, differences from placebo in QTcF were between -4.9 and 3.0 milliseconds at all postdose time points; maximum upper bounds of the one-sided 95% confidence interval for the difference were 5.7 milliseconds for fasiglifam 50 mg and 2.3 milliseconds for fasiglifam 400 mg, meeting predefined criteria for absence of prolongation. Alternate correction methods (Bazett and Individual) showed similar results. Fasiglifam was well tolerated; no subject withdrew due to an adverse event after receiving fasiglifam. In summary, multiple-dose fasiglifam did not affect cardiac repolarization at therapeutic and supratherapeutic doses and was well tolerated in healthy subjects. |
