A Phase 1 Assessment of the QT Interval in Healthy Adults Following Exposure to Rolapitant, a Cancer Supportive Care Antiemetic.

ABSTRACT

This 2-part study evaluated the QT/QTc prolongation potential and safety and pharmacokinetics of the antiemetic rolapitant, a neurokinin-1 receptor antagonist. Part 1 was a randomized, placebo-controlled single-dose-escalation study assessing the safety of a single high dose of rolapitant. Part 2 was a randomized, placebo- and positive-controlled, double-blind parallel-group study including 4 treatment arms rolapitant at the highest safe dose established in part 1, placebo, moxifloxacin 400 mg (positive control), and rolapitant at the presumed therapeutic dose (180 mg). Among 184 adults, rolapitant was absorbed following oral administration under fasting conditions, with a median Tmax of 4 to 6 hours (range, 2-8 hours) and was safe at all doses up to 720 mg. No differences in mean change in QTcF were observed between placebo and rolapitant from baseline or at any point. At any point, the upper bound of the confidence interval for the mean difference between placebo and rolapitant was no greater than 4.4 milliseconds, and the mean difference between placebo and rolapitant was no greater than 1.7 milliseconds, suggesting an insignificant change in QTc with rolapitant. Rolapitant is safe and does not prolong the QT interval at doses up to 720 mg relative to placebo in healthy adults.