Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants.

ABSTRACT: SAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1). This phase I first-in-human healthy participant study (NCT05795907) was comprised of three parts: randomized, double-blind, placebo-controlled single ascending dose (SAD; part 1a); 14-day multiple ascending dose (MAD; part 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SAR443820; and a separate open-label, single-dose part 1b (PK-cerebrospinal fluid [CSF]) to assess SAR443820 levels in CSF. SAR443820 was well-tolerated in healthy participants, and no treatment discontinuation related to an adverse event (AE) occurred. Most common AEs were dizziness and headache. No clinically meaningful changes wer

SUBMITTER: Hincelin-Mery A 

PROVIDER: S-EPMC10772668 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature