Development of a Prototype, Once-Daily, Modified-Release Formulation for the Short Half-Life RIPK1 Inhibitor GSK2982772.

ABSTRACT:

Purpose

GSK2982772 is a selective inhibitor of receptor-interacting protein kinase-1, with a 2-3 h half-life. This study evaluated if a once-daily modified-release formulation of GSK2982772 could be developed with no significant food effect.

Methods

Part A evaluated the pharmacokinetics of GSK2982772 following fasted single-dose (120 mg) administration of two matrix minitab formulations (MT-8 h and MT-12 h) vs 120 mg immediate release (IR) and MT-12 h with a high-fat meal. Part B evaluated once-daily MT-12 h for 3 days at three dose levels. Part C evaluated a matrix monolithic (MM-12 h) formulation at two dose levels in different prandial states.

Results

All modified-release formulations dosed in the fasted state reduced maximum plasma concentration (Cmax), delayed ti

SUBMITTER: Tompson DJ 

PROVIDER: S-EPMC8292240 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature