Objective: Evaluate the tolerability, safety and efficacy of PRAX-944, a selective small molecule T-type calcium channel blocker, for treatment of essential tremor (ET).

Background: Essential tremor is the most common movement disorder with clear need for novel therapies. Approximately 50% of patients seeking pharmacological therapy discontinue medications due to limited efficacy and poor tolerability. We previously demonstrated tolerability of pharmacodynamically-active doses of PRAX-944, up to 120 mg, in healthy participants (ACTRN12620000675921), as well as preliminary evidence of tremor reduction following 20-40 mg PRAX-944 in adults with ET (NCT05021978). The current PRAX-944-222 (Essential1) trial (NCT05021991) further explores the safety and efficacy of 20, 60 and 100 mg once-daily (QD) PRAX-944 in adults with ET.

Method: This 8-week, double-blind, placebo-controlled, randomized, parallel-group study will recruit 112 adults with moderate-to-severe ET defined by upper limb tremor quantified with The Essential Tremor Rating Assessment Scale (TETRAS-UL, score≥10). Eligible participants must be off ET medications or stable on their medication for 1 month prior to screening. Participants will be randomized (1:1:1:1) to titrated doses of 20, 60, or 100 mg PRAX-944 QD or placebo.

Results: The primary endpoint will be incidence and severity of adverse events. Secondary endpoints evaluating efficacy will include baseline to week 8 change in the TETRAS-performance and activities of daily living (ADL) subscales, wearable accelerometry measures and an ET performance-based scale combining clinician scoring of participants as they conduct ADL-related tasks. This trial will inform power calculations and dose selection for later phase trials. Enrolment commenced in late 2021.

Conclusion: Expanding on preliminary findings, the Essential1 trial will further examine the safety, tolerability and efficacy of PRAX-944 in adults with ET, and will determine optimal doses and endpoints for evaluation in later phase studies. Importantly, the unique design seeks to address the sub-optimal benefit-risk profile of current therapies and associated unmet needs in ET.

References: This abstract contains material that has been accepted for presentation at the American Academy of Neurology Annual Meeting; April 2022.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-2-randomized-double-blind-placebo-controlled-trial-of-prax-944-for-the-treatment-of-essential-tremor/