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.
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| 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.
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| Authors | Xiaofei Zhou, Paul Matthias Diderichsen, Neeraj Gupta |
| Journal | Clinical pharmacology in drug development (Clin Pharmacol Drug Dev) Vol. 11 Issue 6 Pg. 770-779 (06 2022) ISSN: 2160-7648 [Electronic] United States |
| PMID | 35187855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2022 Takeda Development Center Americas, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. |
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