| Eligibility |
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.
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