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
References
Jan 1, 1977·Journal of Pharmaceutical Sciences·S M BergeD C Monkhouse
Dec 4, 2001·Genes & Development·P W Ingham, A P McMahon
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Craig D PeacockWilliam Matsui
Jul 17, 2007·Nature Medicine·Christine DierksMarkus Warmuth
Apr 23, 2008·Journal of Pharmaceutical Sciences·Changquan Calvin SunFrancisco J Alvarez
Jan 27, 2009·Nature·Chen ZhaoTannishtha Reya
Jan 10, 2012·Blood·David A Irvine, Mhairi Copland
Jun 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ross McMillan, William Matsui
Jun 29, 2012·Clinical Pharmacology and Therapeutics·N R BudhaJ A Ware
Sep 21, 2013·Molecular Pharmaceutics·Gillian S SmelickJoseph A Ware
Feb 9, 2012·ACS Medicinal Chemistry Letters·Michael J MunchhofGeorge T Tkalcevic
Jun 20, 2014·Cancer Chemotherapy and Pharmacology·M Naveed ShaikWendy J Levin
Dec 22, 2015·The Lancet. Haematology·Giovanni MartinelliCatriona Jamieson
Mar 6, 2017·Critical Reviews in Oncology/hematology·Gianmauro NumicoFausto Roila
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
Sep 25, 2020·Leukemia & Lymphoma·Jorge E CortesMichael Heuser
Nov 27, 2019·Journal of Clinical Pharmacology·Swan LinAna Ruiz-Garcia
Jul 20, 2020·Annals of Hematology·Juan Eduardo Megías-VericatPau Montesinos
Dec 12, 2018·Cancer Chemotherapy and Pharmacology·Naveed ShaikRobert R LaBadie
Mar 24, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Zahari VinarovPatrick Augustijns