A phase 1 open-label study to assess the relative bioavailability of TAK-931 tablets in reference to powder-in-capsule in patients with advanced solid tumors.

Autor:	Steeghs, Neeltje, Pruis, Melinda, van Herpen, Carla, Lu, Vickie, Redman, John, Zhou, Xiaofei
Předmět:	DRUG tablets CONFIDENCE intervals PROTEIN kinase inhibitors PHARMACEUTICAL encapsulation BIOAVAILABILITY ANTINEOPLASTIC agents INVESTIGATIONAL drugs RANDOMIZED controlled trials CANCER patients DESCRIPTIVE statistics RESEARCH funding TUMORS CROSSOVER trials STATISTICAL sampling BIOTRANSFORMATION (Metabolism) POWDERS
Zdroj:	Investigational New Drugs; Feb2023, Vol. 41 Issue 1, p53-59, 7p
Abstrakt:	Summary: 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). [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink