A Phase 2 RCT Study of CX-8998 for Essential Tremor

Inclusion Criteria: 1. Signed informed consent form indicating that the subject has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts. 2. Men or non-pregnant, non-breastfeeding women 18 to 75 years-of-age who are able to read and understand English. 3. Diagnosis of definite or probable essential tremor (ET) as defined by the Tremor Investigational Group with involvement of the hands and arms without present causes of enhanced physiologic tremor (Deuschl et al.,1998). 4. Diagnosis of ET before the age of 65. 5. Tremor severity score of at least 2 in at least one upper extremity on at least one of the three maneuvers on the TETRAS scale. 6. Total TETRAS performance score of at least 15. 7. One concomitant anti-tremor medication (other than primidone) is allowed. Note: Primidone is NOT an allowed anti-tremor medication. If on primidone, subjects are allowed to extend their screening period by 2 weeks (for a total of 6 weeks) and discontinue primidone under the supervision of the investigator. 8. Subjects with reproductive capability including all males and women of child-bearing potential (WOCBP) must agree to practice continuous abstinence or adequate contraception methods (appropriate double barrier method or oral, patch, implant, or injectable contraception) from as soon as feasible during screening period until at least 30 days after the last dose. 9. Approval by the sponsor medical personnel as to final suitability for the study. Exclusion Criteria: 1. Exposure to tremorigenic drugs or drug withdrawal states within the 30 days prior to the first planned dose of study drug. 2. Direct or indirect trauma to the nervous system within 3 months preceding the onset of tremor 3. History or clinical evidence of psychogenic tremor origin 4. Known history of other medical or neurological conditions that may cause or explain subject's tremor, including, but not limited to: a. Parkinson's disease b. dystonia c. cerebellar disease, other than essential tremor d. Traumatic Brain Injury e. alcohol abuse or withdrawal f. mercury poisoning g. hyperthyroidism h. pheochromocytoma i. head trauma or cerebrovascular disease within 3 months prior to the onset of essential tremor j. multiple sclerosis k. polyneuropathy l. family history of Fragile X syndrome 5. Prior MR-guided Focused Ultrasound or surgical intervention (e.g., deep brain stimulation, ablative thalamotomy or gamma knife thalamotomy). 6. Botulinum toxin injection in the 6 months prior to screening. 7. Currently using more than one anti-tremor medication. 8. Experiencing clinical benefit from and/or is not willing to discontinue primidone 9. Use of medication(s) in the past month that might produce tremor or interfere with the evaluation of tremor, such as, but not limited to: CNS-stimulants, lithium, amiodarone, metoclopramide, theophylline, and valproate 10. Inability to refrain from use of medication/substance(s) that might produce tremor or interfere with the evaluation of tremor on study visit days, such as but not limited to stimulant decongestants, beta-agonist bronchodilators, caffeine, alcohol and tobacco, based on Investigator assessment at baseline. 11. Positive urine drug screen. 12. Regular use of more than two units of alcohol per day. 13. Sporadic use of a benzodiazepine, sleep medication or anxiolytic to improve sleep performance. Stable use at a consistent dose is allowed as long as tremor persists against the background of regular medication use. Use on the evening prior to a study visit is prohibited. 14. Use of prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study, including primidone. 15. Concurrent illnesses that would be a contraindication to trial participation, including, but not limited to: a. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening b. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure c. Clinically significant ECG d. Known infection with HIV, hepatitis B, or hepatitis C, unless curative therapy completed for hepatitis C with negative PCR for HCV RNA e. Significant hepatic (AST/ALT \> 2X upper limit of normal) or renal disease (creatinine clearance \<39 mL/min) f. Significant psychiatric history including mood disorders and alcohol or substance abuse within the last year g. A current C-SSRS score of 4 or 5 at screening or history of suicide attempt at any time during the past year h. Clinically significant impaired balance or is considered at increased risk for falls i. Symptomatic orthostatic hypotension. 16. Treatment with an investigational agent within 30 days prior to the first dose of CX-8998 or planning to receive an investigational agent during the study.