Abstract
In this phase 1 open-label study, we assessed the relative bioavailability of a prototype tablet formulation of TAK-931, a cell division cycle 7 kinase inhibitor, in reference to the current powder-in-capsule (PIC) formulation in patients with advanced solid tumors for whom no effective standard treatment was available. Adult patients were randomized 1:1 in a crossover fashion to receive one dose of TAK-931 80 mg PIC on Day 1 and one dose of TAK-931 80 mg tablet on Day 3 (or the reverse sequence), followed by TAK-931 50 mg PIC once daily (QD) for 12 days starting from Day 5, before a 7-day rest period (Cycle 0). From Cycle 1, all patients received 50 mg PIC QD on Days 1–14 followed by a 7-day rest period. Twenty patients were enrolled. Median Tmax was achieved approximately 2 h post-dose of TAK-931 80 mg for both tablet and PIC. Geometric mean Cmax, AUC exposures, and T1/2z of TAK-931 were similar for both formulations. Geometric mean Cmax, AUClast, and AUCinf ratios were 0.936 (90% confidence interval [CI]: 0.808–1.084), 1.004 (90% CI: 0.899–1.120), and 1.007 (90% CI: 0.903–1.123), respectively, for TAK-931 tablet in reference to PIC. Discontinuation of TAK-931 due to treatment-emergent adverse events (TEAEs) occurred in 1 patient. Four (20%) patients experienced a serious TEAE; none were considered related to TAK-931. Pharmacokinetics and systemic exposure profiles were similar following administration of both formulations, supporting the transition from PIC to tablet in the clinical development of TAK-931. (Trial registration numberClinicalTrials.gov NCT03708211. Registration date October 12, 2018).
Original language | English |
---|---|
Pages (from-to) | 53-59 |
Number of pages | 7 |
Journal | Investigational New Drugs |
Volume | 41 |
Issue number | 1 |
DOIs | |
Publication status | Published - Feb 2023 |
Bibliographical note
Funding Information:The authors would like to thank all of the patients who participated in this study and their families, as well as all the investigators and site staff who made the study possible. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Rhian Dyer MSc and Clair Clowes MPhil, of Ashfield MedComms, an Inizio Company, funded by Takeda Pharmaceutical USA, Inc., and complied with the Good Publication Practice-3 (GPP3) guidelines (Battisti WP, et al. Ann Intern Med 2015;163:461–4).
Publisher Copyright:
© 2022, The Author(s).