Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)

Inclusion Criteria:

1. Has a body mass index (BMI) at Screening of ≥18 kg/m2.
2. Has a clinical diagnosis of ET confirmed during screening and characterized bypostural and action tremor.
3. If currently receiving medication prescribed for ET, must be on ≤1 medications, onstable dose(s) for at least 1 month prior to Screening, and willing to maintain stabledose(s) throughout the study. As needed (PRN) use of prescribed ET medicines is notallowed with the exception of propranolol PRN. Participants prescribed propranolol PRNare eligible but must discontinue the PRN dose after the first day of screening.Primidone use is not allowed within 2 weeks prior to screening and throughout durationof study.
4. Women of childbearing potential must undertake pregnancy tests, with a documentednegative serum pregnancy test at Screening, negative urine pregnancy tests at Baseline (Day 1) prior to administration of study drug, throughout the intervention periods (asoutlined in the SoA) and at the SFU or ED Visit, as appropriate.
5. Is willing and able to use contraception as defined in the protocol and ICF.
6. Has been assessed as an appropriate and suitable candidate by investigator and has aneurological exam and medical record(s) consistent with ET diagnosis, as confirmed bythe ERC central reviewer.
7. Confirm key inclusion criteria at Baseline

Exclusion Criteria:

1. Neuropathy, muscle weakness, arthropathy or other musculoskeletal diagnosis of theupper extremity that impairs dexterity or function.
2. Has a known hypersensitivity to any component of the formulation of ulixacaltamide.
3. Is unwilling or unable to refrain from episodic use of medication(s)/substance(s) thatmight interfere with the evaluation of tremor during the study.
4. Is sporadically using a benzodiazepine, sleep medication or anxiolytic (as furtherdefined in the protocol), that in the judgement of the investigator or sponsor wouldconfound the assessment of tremor.
5. Has trauma to the nervous system within 3 months preceding the onset of tremor.
6. Has a history of unilateral tremor or clinical evidence of another medical,neurological, or psychiatric condition that may explain or cause tremor, including butnot limited to Parkinson's disease, Huntington's disease, Alzheimer's disease, strokewith neurologic sequelae, intention tremor (IT) caused by etiology other than ET,cerebellar disease (including spinocerebellar ataxias), primary dystonia, Fragile XTremor/Ataxia syndrome or family history of Fragile X syndrome, traumatic braininjury, psychogenic tremor, alcohol or benzodiazepine abuse or withdrawal, multiplesclerosis, polyneuropathy (diabetic neuropathy allowed if disease does not affect gaitor balance and does not involve upper extremity), and endocrine states such asuncontrolled or inadequately treated hypothyroidism, food, or supplement inducedmovement disorders (e.g., tremor related to beta agonists or caffeine), or othermedical, neurological, or psychiatric conditions that may explain or cause tremor.
7. Has had prior magnetic resonance-guided focused ultrasound or surgical interventionfor ET such as a deep brain stimulator (DBS) or lesion therapy such as thalamotomy.
8. Has had botulinum toxin injection for ET in the 6 months prior to Screening orthroughout the study.
9. Is using the Cala trio health device for ET in 14 days prior to Screening orthroughout the study.
10. Is unwilling or unable to refrain from drinking alcohol 24 hours before and duringclinical study assessments, or regular use of alcohol that would preclude abstinencefrom alcohol for this time period around visits.
11. Has a history of substance use disorder consistent with Diagnostic and StatisticalManual of Mental Disorders Fifth Edition Text Revision (DSM-5-TR) criteria.Participants with a previous diagnosis of substance use disorder who have been inremission for at least 2 years can participate in the study.
12. Is currently pregnant or breastfeeding or is planning to become pregnant during theclinical trial or within 31 days of the last study drug dose.
13. Is currently taking a prescription or non-prescription product(s) and food known to bemoderate or strong inhibitors or strong inducers (moderate inducers are notprohibited) of cytochrome P450 (CYP3A4), which cannot be discontinued at least 5half-lives or 14 days prior (whichever is the longer period of time) to Baseline andwithheld throughout the clinical study.
14. Has received any experimental or investigational drug, device, or other therapy within 30 days or 5 half-lives (whichever is longer) prior to Screening.
15. Has any of the following abnormal test results at Screening: a serum total bilirubinvalue >1.5×upper limit of normal (ULN); a serum alanine aminotransferase (ALT) oraspartate aminotransferase (AST) value >2×ULN. As an exception, participants thatpresent with elevated bilirubin in the absence of elevations in ALT or AST that fitsthe pattern of Gilbert's syndrome may be enrolled after discussion with the medicalmonitor and/or sponsor designee if their conjugated bilirubin is below the ULN.
16. History of human immunodeficiency virus (HIV) infection or positive screening resultfor: HIV 1 or 2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis B coreantibody (HBcAb), or hepatitis C virus antibody (HCVAb).
17. History of long QT syndrome and/or a Fridericia formula corrected QT interval (QTcF)interval >450 msec (males) or >460 msec (females) per electrocardiogram (ECG) done atScreening.
18. Any major psychiatric disorder, including but not limited to depression and anxiety,that is uncontrolled (for the past 90 days) or, in the investigator's judgment, caninterfere with any of the study procedures.
19. Has a lifetime history of any suicide attempt, or suicidal ideation with intent withinthe past 2 years prior to Screening.
20. Participants who have a history of malignancy, myeloproliferative orlymphoproliferative disorders within the past 5 years prior to screen are excluded. Exceptions:

• Participants with completely excised non-melanoma skin cancer (such as basal cellcarcinoma or squamous cell carcinoma) or cervical carcinoma in situ are permittedat any time.
• Participants with a history of other malignancies deemed cured by adequatetreatment are also permitted at any time.

21. Has any other significant disease or disorder including but not limited touncontrolled seizure or epilepsy, diabetes, cardiovascular disease, renal disease,laboratory abnormalities, or environmental factor that, in the opinion of theinvestigator or sponsor designee, may either put the participant at risk due toparticipation in the clinical trial, may influence or confound the result of theclinical trial, or may affect the participant's ability to participate in the clinicaltrial. Uncontrolled epilepsy or seizure is exclusionary and is defined as a seizure orepilepsy diagnosed by a medical clinician and a documented seizure or change inseizure medication (medication or dose) in the last 2 years. An estimated glomerularfiltration rate (eGFR) of <60 using the 2021 Chronic Kidney Disease-Epidemiology (CKD-EPI) formula mL/min/1.73m2 or urine albumin creatinine ratio (uACR) of ≥ 30 mg/gis exclusionary.
22. Participant has a positive alcohol or drug screening (including cannabis andcannabis-derived products). The participant can be enrolled in the study, if they arewilling to stop use of cannabis or cannabis-related products after the Screening Visitand have a negative cannabidiol (CBD) screen result at Baseline (Day 1). A positiveamphetamine, benzodiazepine or opioid drug screening result could be allowed if it isdetermined that the result is a false positive (for example caused by anothermedication), or if the result is due to a documented prescribed medication (forexample: benzodiazepine or opioid) that in the opinion of the investigator or sponsordesignee, is prescribed for a medical condition that aligns with standard of care, isnot associated with substance abuse and the investigator's assessment determines thatthe medical condition and medication dose is stable and expected to remain stablethroughout the trial.
23. History of or evidence of psychogenic tremor
24. Prior participation in an ulixacaltamide clinical trial at any time or other clinicaltrial evaluating a potential drug for ET in the past 6 months (with the exception ofparticipants with documentation that they received placebo treatment only), with theexception of participants that are currently enrolled in and complete the EOT visit inPRAX-944-222 extension period.