Assessment of Effects of Investigational TAK-931, an Oral Cell Division Cycle 7 Kinase Inhibitor on the QTc Intervals in Patients With Advanced Solid Tumors.

Abstract

TAK‐931, a novel, selective, small‐molecule inhibitor of cell division cycle 7 has been investigated in multiple clinical trials in patients with advanced solid tumors. An integrated analysis using data from 2 clinical studies assessed effects of TAK‐931 on electrocardiogram QT intervals and heart rate (HR). Pharmacokinetic samples and matched triplicate electrocardiogram data were collected in 48 patients with cancer receiving oral administration of TAK‐931 50 or 80 mg once daily. The relationships between TAK‐931 plasma concentrations and the HR‐corrected QT interval via Fridericia (QTcF) or population (QTcP) and HR were analyzed using linear mixed‐effects models with fixed effects for day and time. At the geometric mean maximum TAK‐931 plasma concentrations after administration of 50 mg, an HR change of 3.40 beats per minute (90%CI, 1.86‐4.80) was predicted. Change in QTcF of −3.41 milliseconds (90%CI, −5.77 to −1.17) and QTcP of −2.02 milliseconds (90%CI, −4.15 to 0.0679) were estimated, indicating there was no effect of TAK‐931 on the QT intervals at a recommended phase 2 dose of 50 mg once daily for 14 days in a 21‐day cycle.