Efficacy and Safety of Ulixacaltamide in Essential Tremor: Topline Phase 3 Results from Essential3 Study 1 (Parallel-Design Study) (P5-17.002)

Objective Evaluating the efficacy, safety, and tolerability of ulixacaltamide vs. placebo in adults with essential tremor (ET) as part of the pivotal Phase 3 Essential3 Program. Background An estimated 7 million people in the US live with ET, a progressive neurologic disorder with involuntary tremor presenting significant disruption to daily activities and quality-of-life. Existing treatment options are limited, with high discontinuation rates due to poor tolerability and limited efficacy. Ulixacaltamide is a selective T-type calcium channel (TTCC) modulator in development for ET. The Essential3 Program comprised two simultaneous 12-week registrational studies, with blinded assignment: Study 1 (parallel-group design) and Study 2 (randomized withdrawal), conducted using a decentralized model, with optional long-term safety extension. Design/Methods Study 1 was a randomized, double-blind, placebo-controlled trial enrolling participants aged 18–85 years with ET (symptoms ≥3 years; if on ET medication(s), stable dose for ≥28 days prior to screening). Participants were randomized 1:1 to ulixacaltamide hydrochloride 60mg QD (after 2-week titration) or placebo for 12 weeks. The primary endpoint was change from baseline to Day 56 in mADL11 (TETRAS-ADL items 1–11 with modified score). Secondary endpoints included rate of disease improvement and Patient/Clinical Global Impression scores. Safety assessments included TEAEs, labs, ECGs. Results A total of 473 participants were enrolled. The primary endpoint was met, with topline results to be presented. Conclusions Essential3 is the only ongoing Phase 3 Program in ET, with Study 1 representing the first registrational study exploring the efficacy and tolerability of pharmacologic TTCC modulation with ulixacaltamide. Topline results are anticipated to significantly redefine the ET treatment landscape. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff. Disclosure: The institution of Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cala Health. The institution of Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda. The institution of Dr. Brillman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. The institution of Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. The institution of Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for USWorldMeds. Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Brillman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acorda. Dr. Brillman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Acadia. Dr. Brillman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Adamas. Dr. Brillman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for USWorld Meds. Dr. Brillman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Shtilbans has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis Medicine. Dr. Shtilbans has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal Pharmaceuticals. Dr. Shtilbans has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Shtilbans has received research support from Praxis Medicine. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Supernus. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurocrine. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acadia. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbvie. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. Dr. Farmer has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Live. The institution of Dr. Farmer has received research support from Parkinson's Foundation. Dr. Giroux has received personal compensation for serving as an employee of Praxis Precision Medicine. Dr. Giroux has or had stock in Praxis Precision Medicines.Mrs. Fridley has received personal compensation for serving as an employee of Praxis Precision Medicines, Inc. Mrs. Fridley has stock in Praxis Precision Medicines, Inc. Dr. Crimin has received personal compensation for serving as an employee of Praxis Precision Medicine. Dr. Crimin has received personal compensation for serving as an employee of Biohaven. Dr. Crimin has stock in Biohaven. Dr. Crimin has stock in Praxis Precision Medicine. Mr. Tang has nothing to disclose. Mrs. Crush has received personal compensation for serving as an employee of Praxis Precision Medicines. Mrs. Crush has stock in Praxis Precision Medicines . Author has nothing to discloseDr. Petrou has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Petrou has stock in Praxis Precision Medicines. The institution of Dr. Petrou has received research support from Praxis Precision Medicines. Dr. Petrou has received intellectual property interests from a discovery or technology relating to health care. Alyssa Wyant has received personal compensation for serving as an employee of Praxis Precision Medicines. Alyssa Wyant has stock in Praxis Precision Medicines. Alyssa Wyant has received intellectual property interests from a discovery or technology relating to health care. Megan Sniecinski has received personal compensation for serving as an employee of Praxis Precision Medicines. Megan Sniecinski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Praxis Precision Medicines. Marcio Souza has received personal compensation for serving as an employee of Praxis Precision Medicines.