Evaluation of the effect of new formulation, food, or a proton pump inhibitor on the relative bioavailability of the smoothened inhibitor glasdegib (PF-04449913) in healthy volunteers

Cancer Chemotherapy and Pharmacology
Nagdeep GiriM Naveed Shaik

Abstract

This phase I open-label study investigated the oral bioavailability of two novel maleate salt-based glasdegib (PF-04449913) tablet formulations (small- and large-particle size) relative to the current clinical formulation (diHCl salt-based). In addition, the effect of a gastric pH-altering agent (rabeprazole) and food on the pharmacokinetics of the large-particle size formulation of glasdegib were evaluated. The pharmacokinetics of glasdegib oral solution was also assessed. Thirty-four healthy subjects received glasdegib 100 mg as three different formulations in the fasted state (diHCl salt or small- or large-particle size maleate formulation); 13 received the large-particle maleate formulation (fed), and 14 concurrently with rabeprazole (fasted); six subjects received glasdegib 50 mg oral solution (fasted). For both new tablet formulations of glasdegib, ratios (Test:Reference) of adjusted geometric means (90% confidence interval) of area under the concentration-time curve from 0 to infinity and maximum plasma concentration were within 80-125% compared with the diHCl formulation (fasted). For the large-particle size formulation (fed), these ratios were 86.3% (81.0-92.0%) and 75.7% (65.3-87.7%), respectively, compared with faste...Continue Reading

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Citations

Mar 1, 2018·British Journal of Clinical Pharmacology·M Naveed ShaikRobert R LaBadie
Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Richard L Carpenter, Haimanti Ray
Apr 13, 2019·Clinical Pharmacology in Drug Development·Naveed ShaikRobert Roland LaBadie
Aug 23, 2019·Future Oncology·Anna Wolska-Washer, Tadeusz Robak
Feb 7, 2020·Expert Opinion on Pharmacotherapy·Xavier Thomas, Maël Heiblig
Jul 20, 2020·Annals of Hematology·Juan Eduardo Megías-VericatPau Montesinos
Mar 24, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Zahari VinarovPatrick Augustijns

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