Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor

Clin Pharmacol Ther. 2019 Feb;105(2):376-387. doi: 10.1002/cpt.1047. Epub 2018 Mar 23.

Abstract

Model-informed drug development (MIDD) was central to the development of the oral proteasome inhibitor ixazomib, facilitating internal decisions (switch from body surface area (BSA)-based to fixed dosing, inclusive phase III trials, portfolio prioritization of ixazomib-based combinations, phase III dose for maintenance treatment), regulatory review (model-informed QT analysis, benefit-risk of 4 mg dose), and product labeling (absolute bioavailability and intrinsic/extrinsic factors). This review discusses the impact of MIDD in enabling patient-centric therapeutic optimization during the development of ixazomib.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Boron Compounds / pharmacokinetics
  • Boron Compounds / pharmacology
  • Boron Compounds / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Drug Development
  • Glycine / analogs & derivatives*
  • Glycine / pharmacokinetics
  • Glycine / pharmacology
  • Glycine / therapeutic use
  • Humans
  • Models, Theoretical
  • Multiple Myeloma / drug therapy
  • Proteasome Inhibitors / pharmacokinetics
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use*

Substances

  • Boron Compounds
  • Proteasome Inhibitors
  • ixazomib
  • Glycine