Evaluation of the Effect of Momelotinib on Cardiac Repolarization: A Thorough QT Study.

Abstract

A randomized, partially blinded, placebo-controlled, crossover study in 48 healthy adults assessed the effect of momelotinib on the heart rate-corrected QT interval (QTc) using the Fridericia formula (QTcF). QTc was evaluated for momelotinib 200 mg (therapeutic dose), momelotinib 800 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), and placebo. Pharmacokinetic profiles of momelotinib and its active metabolite M21 were evaluated. Momelotinib did not prolong QTcF, as the upper bounds of the 2-sided 90% confidence intervals (CIs) for the mean difference between doses of momelotinib and placebo were <10 milliseconds at all time points. The lower limit of the 2-sided 98% CI for the mean difference in QTcF between moxifloxacin versus placebo was >5 milliseconds at 2, 3, and 4 hours after dosing, demonstrating assay sensitivity. There was no positive relationship between momelotinib plasma concentrations and QTcF. Adverse events (AEs) were more frequent with the supratherapeutic dose of momelotinib, but none were considered severe. There were no deaths, serious AEs, or AEs leading to study discontinuation. Neither therapeutic nor supratherapeutic doses of momelotinib led to clinically significant effects on the QTc interval, supporting a negative finding for QTc prolongation from this thorough QT study.