(409) A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety and Efficacy of NYX-2925 in Subjects with Painful Diabetic Peripheral Neuropathy

NYX-2925, a novel small-molecule modulator of the N-methyl-D-aspartate receptor (NMDAR), was evaluated in a randomized, double-blind, placebo-controlled study, in which 302 subjects with painful DPN received daily oral doses of placebo or NYX-2925 at 10mg, 50mg, or 200mg for four weeks (NCT03219320). This first-in-patient study was conducted across 35 U.S.-based sites and subjects were randomized in a 1:1:1:1 ratio. Average pain intensity was collected using the 11-point Numerical Rating Scale and subjects were assessed for randomization eligibility using a proprietary algorithm employed to improve assay sensitivity. All subjects in the study had moderate to severe pain at baseline. The primary endpoint of the study was the mean change from baseline to week-four of treatment in average daily pain. All dose levels of NYX-2925 resulted in improvements in pain scores from baseline, the largest improvement occurring in the 50mg group – a 1.61-point reduction from baseline. This improvement was numerically, but not statistically, superior to placebo. No plateau in the effect of NYX-2925 at 50mg was observed by the end of this four-week study, suggesting a longer treatment duration may result in continuing improvement in the analgesic effect. Clinically meaningful trends of improvement on key secondary endpoints, including sleep interference and pain on walking were also observed. In a pre-specified analysis of subjects who were not taking a concomitant analgesic medication, those treated with NYX-2925 across all dose levels showed improvements relative to placebo on pain and other endpoints that were greater than those observed in the overall study population. NYX-2925 exhibited favorable safety and was well-tolerated in the study with no serious adverse events. While statistically significant separation from placebo was not achieved on the primary endpoint, information on both the safety and efficacy of NYX-2925 was obtained, which can guide further development of NYX-2925 in chronic pain disorders.