NYX-2925, a Novel N-methyl-D-aspartate Receptor Modulator: A First-in-Human, Randomized, Double-blind Study of Safety and Pharmacokinetics in Adults.

NYX-2925, a new chemical entity, acts as a co-agonist to glutamate at the N-methyl-D-aspartate receptor (NMDAR). At low concentrations of endogenous agonists (glycine/D-serine), NYX-2925 partially activates NMDARs, modulating neural pathways relevant for chronic pain. NYX-2925 is being developed for the treatment of chronic pain conditions, including painful diabetic peripheral neuropathy and fibromyalgia. In this first-in-human, Phase 1, single- (50-1200 mg) and multiple-ascending dose (150-900 mg) study, the safety, tolerability, and pharmacokinetics of NYX-2925 were evaluated in 84 healthy adult volunteers. No safety concerns emerged, including no dissociative side effects. NYX-2925 exhibited dose-proportional pharmacokinetics and minimal accumulation following once-daily dosing for seven days. Cerebrospinal fluid (CSF) measurements confirmed that NYX-2925 crosses the blood brain barrier, with maximum CSF concentrations approximating 6-9% of maximum plasma concentrations at the same dose level. NYX-2925 was safe and well-tolerated in healthy volunteers, and the study results support the continued clinical development for chronic pain conditions. This article is protected by copyright. All rights reserved.