PRAX-944-221: a Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults with Essential Tremor

Objective: We present preliminary findings from PRAX‐944‐221, a Phase 2 clinical trial evaluating efficacy, safety, tolerability, and pharmacokinetics of PRAX‐944 in adults with essential tremor (ET). Background: ET is the most common movement disorder with high unmet patient needs. Treatment options are limited, with high discontinuation rates due to poor tolerability and modest efficacy. PRAX‐944 is a novel selective T‐type calcium channel blocker currently in clinical development for the treatment of ET. Design/Methods: PRAX‐944‐221 is an ongoing, open‐label, 2‐part trial in adults (18‐75 years) with ET (NCT05021978). In Part A, participants received PRAX‐944 20 mg orally once‐daily for 7 days, followed by 40 mg orally once‐daily for 7 days. Eligible participants were receiving either no medications or 1 stable dose tremor medication. The primary outcome was upper limb tremor assessed by The Essential Tremor Rating Assessment Scale (TETRAS‐UL). Secondary outcomes included other measures of tremor severity, as well as safety and tolerability. Results: Seven participants received PRAX‐944 in Part A, with 6 completing all study visits. Mean baseline TETRAS‐UL score was 12.4 (range 10‐15; corresponding to moderate disease). Five (83%) participants included in efficacy analysis were taking concomitant propranolol during the intervention period. Preliminary results revealed a mean reduction in TETRAS‐UL score of 2.83 points on Day 14, corresponding to a 42% reduction in upper limb tremor amplitude. PRAX‐944 20 and 40 mg doses were generally well‐tolerated. Conclusions: Findings from the PRAX‐944‐221 trial provide preliminary evidence that PRAX944 can reduce tremor symptoms of ET at well‐tolerated doses. Continuing investigations, including an expanded dose range up to 120 mg daily with a placebo arm (PRAX‐944‐221 Part B), as well as an 8‐week, dose‐range finding, placebo‐controlled trial (PRAX‐944‐222, NCT05021991) will determine optimal doses of PRAX‐944 for evaluation in later phase studies.