Objective:

Evaluate the efficacy, safety and tolerability of ulixacaltamide (PRAX-944) in Parkinson’s Disease (PD) with motor fluctuations.

Background:

PD, one of the two most common movement disorders, is characterized by bradykinesia, rigidity and resting tremor. Degeneration of nigral dopaminergic neurons results in dopamine loss and is associated with aberrant burst firing in basal ganglia circuits. Dopamine replacement therapy represents the mainstay of PD treatment, although not without potential side effects. Surgical therapy, namely deep brain stimulation (DBS), can be very successful for refractory tremor and motor complications. However, its associated risks highlight the need for a pharmacological agent capable of noninvasively recapitulating the effects of DBS. T-type calcium channel (TTCC) blockade is a promising therapeutic approach with the potential to normalize burst firing and ameliorate motor symptoms in PD. Ulixacaltamide is a novel TTCC blocker in development for the treatment of PD.

Design/Methods:

PRAX-944-231 is a double-blind, placebo-controlled, randomized, parallel-group study that will recruit ~112 adults (30-80 years) with a PD diagnosis consistent with UK Brain Bank and Movement Disorder Society (MDS) criteria, and Hoehn & Yahr staging <4 (ON state) and ≥2.5hours of daily motor off time. Eligible participants must be on stable anti-Parkinsonian oral medication for ≥4 weeks. Participants will be randomized 1:1 to a fixed-dose titration regimen of ulixacaltamide (7-week titration, 4-week maintenance at 100 mg QAM, 2-week taper down) or placebo.

Results:

The primary endpoint will be change from baseline to Day 77 in the MDS - Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score (OFF state). Secondary endpoints will include change from baseline to Day 77 in the MDS-UPDRS Part III tremor sub-score (OFF state) and Part II score; and Patient Global Impression of Severity and Clinician Global Impression of Severity. 

Conclusions:

The PRAX-944-231 trial is expected to provide proof-of-concept for use of ulixacaltamide in the treatment of PD.