Aptinyx reports results from NYX-2925 studies.
Aptinyx announced that exploratory clinical studies of its novel NMDA receptor, or NMDAr, modulator, NYX-2925, provide the first evidence that oral dosing of the product candidate induces pharmacodynamic activities in humans that are understood to be NMDAr-mediated. The two exploratory studies in healthy human volunteers employed electrophysiological measures to assess the pharmacodynamic effects of NYX-2925 at dose levels consistent with those under evaluation in ongoing Phase 2 studies. The findings from these exploratory studies reinforce observations in preclinical mechanistic studies of NYX-2925. The study results validate that NYX-2925 activates NMDAr-mediated pathways, provide further insight into its mechanism of action, and identify potential biomarkers for further investigation. In the first exploratory study, Aptinyx utilized advanced electrophysiology measures in 32 healthy human subjects to evaluate the effects of a single administration of NYX-2925 versus placebo on synaptic plasticity, a biological measure of changes in neural cell communication. Electrical activity within the brain was recorded through multiple electrodes placed on the scalp. This electrical activity can occur at different frequencies and with different magnitude over time. Different patterns observed in response to particular forms of sensory stimuli correspond to activities related to sensory processing, plasticity, learning, and memory. As demonstrated by differences in electroencephalography, or EEG, wave-form responses, administration of NYX-2925 results in robust enhancements in synaptic plasticity. This observed plasticity enhancement, which is consistent with NMDAr pathway activation, was statistically significant two hours following administration and was observed across all dose levels studied. In addition, analysis of time-frequency EEG measures revealed an effect of NYX-2925 on enhanced stimulus processing that persisted for at least seven days. Both the immediate and long-lasting effects on synaptic plasticity are consistent with observations in preclinical studies of NYX-2925. In the second exploratory study, Aptinyx used polysomnography and other measures to evaluate the effects of NYX-2925 on multiple components of sleep, which are also mediated through the NMDAr pathway. Polysomnography evaluates multiple parameters, including electrical activity in the brain. Together, these measures can indicate different states of sleep, including REM and non-REM. Twenty-seven healthy male participants were subjected to sleep disruption and evaluated in a two-arm crossover design study. One arm of the study, in which subjects received NYX-2925 followed by placebo, showed unexpectedly high variability within the small sample size, thus precluding analysis of this arm. However, analysis of the other arm, in which subjects received placebo followed by NYX-2925, showed that NYX-2925 significantly enhanced various measures, including overall sleep duration and non-REM sleep duration. These results are consistent with observations in preclinical studies of NYX-2925 in sleep-disrupted rodents.
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|Article Type:||Clinical report|
|Date:||Nov 12, 2018|
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