Abstract Details

Title PRAX-562-101: A Phase 1 Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of PRAX-562 in Healthy Volunteers

Topic Child Neurology and Developmental Neurology

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 4-011

Objective

We report findings from a first-in-human trial evaluating safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of PRAX-562, as well as the effect of food on PK of a single dose in healthy adults.

Background

PRAX-562 is a next-generation sodium channel blocker in development for treatment of DEEs with a unique profile that may translate to improved tolerability over standard-of-care.

Design/Methods

PRAX-562-101 was a Phase 1 trial in healthy participants aged 18–55 years. Parts A (n=64) and B (n=32) were randomized, placebo-controlled and evaluated single (2.5–150mg) and multiple (30–120mg, 14 days QD) ascending oral doses of PRAX-562, respectively. Part C (n=16) was an open-label, randomized, crossover design evaluating the PK of a single oral dose (90mg) in fasted and fed states. Part C participants were randomized to receive PRAX-562 in the fed (following a high-fat/high calorie meal) or fasted (≥10h after the last, and 4h before the next, meal) state.

Results

112 participants were enrolled (n=88 PRAX-562, n=24 placebo). PRAX-562 was well-tolerated with no clinically significant safety findings in vital signs, laboratory results, physical exams, ECGs, or C-SSRS data; TEAEs were mostly mild (>92%).

Exposure increased dose proportionally over the evaluated dose range. PRAX-562 rapidly appeared in plasma with time to C_max between 2–3h, and detectable levels over a dose interval. 90mg in the fed state resulted in a slight increase in C_max (9%), delay in t_max (4 vs. 2.5h), and modest increase in AUC (14%) vs. the fasted state.

Conclusions

PRAX-562 was well tolerated in healthy participants at single doses up to 150mg (fasted) in Part A, at multiple doses up to 120mg QD for 14 days (fasted) in Part B, and at a single dose of 90mg in fed and fasted states in Part C. Our findings suggest that PRAX-562 can be administered without regard for food.

Authors/Disclosures
Brian Pfister PRESENTER	Dr. Pfister has received personal compensation for serving as an employee of Praxis Precisions Medicines. Dr. Pfister has stock in Praxis Precision Medicines.
Rajeshwari Mahalingam, MD	Dr. Mahalingam has nothing to disclose.
Michael S. Oldham, MD, MPH	Dr. Oldham has received personal compensation for serving as an employee of Praxis Precision Medicines.
	No disclosure on file
Henry Jacotin (Praxis)	Henry Jacotin has received personal compensation for serving as an employee of Praxis Precision Medicines. Henry Jacotin has stock in Praxis Precision Medicines. Henry Jacotin has stock in Clover Health. Henry Jacotin has stock in Certara. Henry Jacotin has stock in Takeda. Henry Jacotin has received personal compensation in the range of $500,000-$999,999 for serving as a VP Clinical Development and Pharmacovigilance with Praxis Precision Medicines.
	No disclosure on file
Corey Puryear, PhD (Praxis Precision Medicines)	Dr. Puryear has received personal compensation for serving as an employee of Praxis Precision Medicine. Dr. Puryear has stock in Praxis Precision Medicines.
Bernard M. Ravina, MD, MSCE (Voyager Therapeutics, Inc.)	Dr. Ravina has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Ravina has stock in Praxis.
Marcio Souza	Marcio Souza has received personal compensation for serving as an employee of Praxis Precision Medicines.
	No disclosure on file

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