Objective:

Evaluating the safety, tolerability and pharmacokinetics of vormatrigine (PRAX-628).

Background:

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 and 30 mg, respectively. This update is from the MAD cohort up to 45mg, and includes the food effect data from Part C.

Design/Methods:

PRAX-628-101, a first-in-human Phase 1 trial, enrolled healthy participants aged 18 to 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 30mg 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.

Results:

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 45mg. Food effect analysis revealed no clinically significant impact to Cmax or AUC at steady state.

Conclusions:

Vormatrigine demonstrated consistent safety, tolerability, and PK profiles, with no significant food effect. These results support flexible dosing regimens up to 45mg in the ongoing vormatrigine ENERGY program.