Neuropathic pain affects ~ 6.9-10% of the general population and leads to loss of function, anxiety, depression, sleep disturbance, and impaired cognition. Here we report the safety, tolerability, and pharmacokinetics of a voltage- and use-dependent sodium channel blocker, vixotrigine, currently under investigation for the treatment of neuropathic pain conditions. The randomized, placebo-controlled, phase I clinical trials were split into single (SAD) and multiple ascending dose (MAD) studies. Healthy volunteers received oral vixotrigine as either single doses followed by a ≥ 7-day washout period for up to five dosing sessions (SAD, n = 30), or repeat doses (once or twice daily) for 14 and 28 days (MAD, n = 51). Adverse events (AEs), maximum observed vixotrigine plasma concentration (C ), area under the concentration-time curve from predose to 24 hours postdose (AUC ), time to C (T ), and terminal half-life (t ), among others, were assessed. Drug-related AEs were reported in 47% and 53% of volunteers in the SAD and MAD studies, respectively, with dizziness as the most commonly reported drug-related AE. SAD results showed that C and AUC increased with dose, T was 1-2 hours, and t was ~ 11 hours. A two-fold increase in accumulation was observed when vixotrigine was taken twice vs. once daily (MAD). Steady state was achieved from day 5 onward. These data indicate that oral vixotrigine is well tolerated when administered as single doses up to 825 mg and multiple doses up to 450 mg twice daily.