Characterizing the Sources of Pharmacokinetic Variability for TAK-117 (Serabelisib), an Investigational Phosphoinositide 3-Kinase Alpha Inhibitor: A Clinical Biopharmaceutics Study to Inform Development Strategy

Clinical Pharmacology in Drug Development
Chirag PatelKarthik Venkatakrishnan

Abstract

TAK-117 (also known as MLN1117 or serabelisib) is an orally available inhibitor of phosphoinositide 3-kinase alpha being developed for treatment of solid tumors. This clinical study in healthy subjects assessed the relative bioavailability of a TAK-117 tablet compared with a capsule formulation (part 1) and the effect of food (part 2) and intragastric pH modulation (part 3) on TAK-117 pharmacokinetics. In part 1, subjects received single doses of 900 mg TAK-117 under fasting conditions as capsules and tablets on 2 different occasions in random order. In part 2, subjects received a single dose of 600 mg TAK-117 under fed (high-fat meal) or fasted conditions on 2 different occasions in random order. In part 3, subjects received a single dose of 900 mg TAK-117 alone and in combination with lansoprazole in a fixed sequence. Blood samples were collected up to 72 hours after each TAK-117 dose. The geometric mean ratios (90% confidence intervals) for the area under the TAK-117 plasma concentration-time curves were 1.53 (0.93-2.51) for tablets versus capsules, 1.50 (1.00-2.25) for fed versus fasted, and 0.02 (0.01-0.04) for TAK-117 plus lansoprazole compared with TAK-117 alone. The most common adverse event was nausea, the incidence of...Continue Reading

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Citations

Sep 13, 2019·Journal of Clinical Pharmacology·Misaki SuzukiSriram Krishnaswami
Nov 2, 2019·Clinical and Translational Science·Mariam A AhmedDaria Stypinski
Jan 7, 2020·Current Topics in Medicinal Chemistry·Rammohan R Y Bheemanaboina
Nov 5, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Urvi H GalaRobert O Williams
Oct 31, 2018·Molecular Pharmaceutics·Hywel D WilliamsChristopher J H Porter

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