A Clinical Study to Evaluate CAD-1883 in Essential Tremor
Condition: Essential Tremor
MeSH terms: Tremor; Essential Tremor
Intervention: CAD-1883
Intervention description: Treatment groups receiving twice-daily oral dosing of CAD-1883 for a treatment period of 14 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: ET; Essential Tremor

Summary:

      This is an open-label study designed to evaluate the safety, tolerability and efficacy of
      CAD-1883, a positive allosteric modulator of the SK channel, administered twice daily orally
      to adult patients with ET. Patients with the diagnosis of ET based on the Movement Disorder
      Society (MDS) criteria with a documented severity of tremor based on the
      clinician-administered TETRAS Performance Subscale are eligible to be enrolled in the study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult subjects aged between 18 and 75 years old, inclusive, with history of tremor
             that fulfills the diagnostic criteria of ET according to Movement Disorder Society
             (MDS) Consensus Statement on the classification of tremors from the task force on
             tremor of the International Parkinson and Movement Disorder Society (Bhatia, 2018).

          2. Duration of ET illness since the first symptoms were noticeable of at least 3 years or
             more prior to screening, based on the subject's self-report, with onset prior to age
             65 years old, per the Principal Investigator's assessment during screening.

          3. Except for ET, subjects must be otherwise healthy as determined by the Investigator,
             based upon a medical evaluation including medical history, physical examination,
             laboratory tests, and 12-lead ECG.

          4. Subjects are able to understand study activities required, can give written informed
             consent, and are willing to comply with the requirements and restrictions of the
             study.

          5. Women of childbearing potential must undertake a pregnancy test with documented
             negative serum pregnancy test at Screening and negative urine pregnancy test result at
             Pre-dose, Days 7 and 14 before administration of the study drug, and then at the
             Follow-up visit (Day 21).

          6. Postmenopausal women must have had ≥365 days of spontaneous amenorrhea, with
             documented follicle-stimulating hormone (FSH) ≥38 IU/mL, prior to screening. If
             needed, per Investigator's judgment, FSH level can be performed at Screening.

          7. Surgically sterile women must have documentation of a hysterectomy, bilateral
             ovariectomy, or bilateral tubal ligation.

          8. Female subjects with reproductive potential and male subjects with reproductive
             potential or who have female partners of reproductive potential, must agree to use two
             effective methods of contraception from signing informed consent until 90 days after
             the last dose of study drug. Acceptable forms of contraception include double barrier
             (ie, condom with spermicide); surgically sterilized partner (180-day minimum); or
             abstinence.

        Exclusion Criteria:

          1. Prior or ongoing medical condition or any abnormal finding on the Screening visit
             physical exam, ECG, laboratory testing that, in the Investigator's opinion, could
             adversely affect the safety of the subject or the conduct of the study assessments.

          2. Any neurological abnormality other than ET upon neurological exam, including dystonia,
             ataxia, or any other neurodegenerative disease, including multiple sclerosis or
             Parkinson's disease.

          3. Significant cognitive impairment or dementia that, in the opinion of the Investigator,
             would interfere with participation in the study.

          4. An unstable thyroid condition that, per the Investigator's judgment, has not
             stabilized over the past 90 days prior to screening. This includes current clinical
             history of hypo- or hyperthyroidism, thyrotoxicosis or significant abnormality of
             thyroid function testing at Screening.

          5. History of, or evidence of psychogenic tremor at Screening.

          6. History of anaphylaxis, hypersensitivity reactions (including to any of CAD-1883
             excipients), or clinically significant drug allergies.

          7. Alkaline phosphatase, aspartate aminotransferase (AST), and/or alanine
             aminotransferase (ALT) level >2.0 x upper limit of normal (ULN) at Screening and/or at
             Pre-dose.

          8. Serum creatinine >120 μmol/L and/or creatinine clearance <60 mL/min (according to
             Cockcroft-Gault formula) at Screening and/or at Pre-dose.

          9. Total bilirubin >2.0 x ULN at Screening and/or at Pre-dose. Note: isolated bilirubin
             >2.0 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%.

         10. History of Long QT syndrome and/or QTcF (Fridericia's correction) interval >450 msec
             (males) or >470 msec (females) per 12-lead ECG done at Screening.

         11. History of Alcohol Use Disorder per Diagnostic Statistical Manual of Mental Disorders,
             Fifth Edition (DSM-V) criteria.

         12. History of human immunodeficiency virus (HIV) infection or positive screening result
             for: HIV 1 or 2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis B core
             antibody (HBcAb), or hepatitis C virus antibody (HCVAb).

         13. Has a diagnosis of epilepsy or any history of seizure as an adult, head trauma,
             stroke, transient ischemic attack within 1 year prior to Screening, unexplained loss
             of consciousness within 1 year prior to Screening, or any lifetime history of
             asymptomatic or symptomatic orthostatic hypotension (eg, postural syncope).

         14. History of unstable angina, myocardial infarction, chronic heart failure (New York
             Heart Association Class 3 or 4), or clinically significant conduction abnormalities
             (eg, unstable atrial fibrillation) within 1 year prior to screening.

         15. Any major psychiatric disorder that is uncontrolled (for the past 90 days) that, per
             the Investigator's judgment, can interfere with any of the study procedures.

         16. Subject has cancer, except for the following: basal cell carcinoma or successfully
             treated squamous cell carcinoma of the skin; cervical carcinoma in situ; prostatic
             carcinoma in situ; or other malignancies curatively treated and with no evidence of
             disease recurrence for at least 3 years.

         17. Subjects with scheduled surgeries during the study period.