PRAX-562-101: A Phase 1 Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of PRAX-562 in Healthy Volunteers
Rajeshwari Mahalingam1, Michael Oldham1, Marjie Hard1, Bernard Ravina1
1Praxis Precision Medicines
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 Cmax between 2–3h, and detectable levels over a dose interval. 90mg in the fed state resulted in a slight increase in Cmax (9%), delay in tmax (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.