Evaluating the safety, tolerability and pharmacokinetics (PK) of vormatrigine (PRAX-628).
Preliminary PK findings from PRAX-628-101 Part A (single ascending doses, SAD) and Part B (multiple ascending doses, MAD) demonstrated a favorable safety and tolerability profile in doses up to 45 mg. This update is from the MAD cohort up to 45 mg, and includes the food effect data from Part C.
PRAX-628-101, a first-in-human Phase 1 trial, enrolled healthy participants aged 18-55 years. Parts A and B were randomized, double-blinded, and placebo-controlled, with participants randomized 3:1 to receive vormatrigine or placebo under fasting conditions. SAD cohorts received single doses starting at 5mg and MAD cohorts received daily doses for 10 days. Part C utilized a randomized, open-label, crossover design with participants receiving two 30 mg doses (fasted and fed states) separated by a 7-day washout. Safety and tolerability assessments included adverse events (AEs), vital signs, 12-lead ECGs, physical examinations, clinical laboratory tests, and the Columbia-Suicide Severity Rating Scale (MAD only). Plasma PK parameters were analyzed.
52 healthy participants completed Parts A (n=18), B (n=18) and C (n=16). Vormatrigine was well tolerated with AEs mostly mild, transient, and self-resolving. PK data showed dose-dependent exposure proportional to dose increases up to 45 mg. Food effect analysis revealed no clinically significant impact to Cmax or AUC at steady state. Consistent with data from Part B 20 and 30 mg cohorts, concentrations exceeding the predicted efficacious level based on the mouse MES EC50 were reached in the 45 mg cohort.
Vormatrigine demonstrated consistent safety, tolerability, and PK profiles, with no significant food effect. Findings from the 45 mg cohort highlight the highest multiples of the predicted therapeutically effective concentration achieved to date, with expected translation to patient benefit. These results support flexible dosing regimens up to 45 mg in the ongoing vormatrigine ENERGY program.