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 I, single‐ascending dose (50–1,200 mg) and multiple‐ascending dose (150–900 mg) study, the safety, tolerability, and pharmacokinetics (PKs) of NYX‐2925 were evaluated in 84 healthy adult volunteers. No safety concerns emerged, including no dissociative side effects. NYX‐2925 exhibited dose‐proportional PKs and minimal accumulation following once‐daily dosing for 7 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.