Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK-001 using a randomized, double-blind, placebo-controlled study design.

ABSTRACT: ESK-001 is a highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2), which plays an essential role in mediating cytokine signaling in multiple immune-mediated diseases. In 2 phase I studies, a first-in-human single ascending dose (SAD) and multiple ascending dose (MAD) study and a multiple-dose (MD) study, we evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered ESK-001 in healthy participants using a randomized, double-blind, placebo-controlled study design. ESK-001 was rapidly absorbed with systemic exposures generally increasing dose-proportionally across all cohorts. The mean terminal half-life ranged from 8 to 13 h with no to minimal accumulation of ESK-001 following q.d. doses and ~2-fold accumulation following Q12 dose

SUBMITTER: Ucpinar S 

PROVIDER: S-EPMC11602527 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature