Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics And Pharmacodynamics of SIF001 in Healthy Subjects and in Epilepsy Patients

Exclusion Criteria

• •Healthy Volunteers (Stage I and II (Phase 1a and 1b)):
• •1. Subjects with any unresolved history of clinically significant disease, in the opinion of the investigator.
• •2. Past or intended use of over-the-counter (OTC) or prescription medication (other than ≤ 2 g/day paracetamol \[acetaminophen\] or ≤ 800-mg/day ibuprofen), vitamins, and dietary or herbal supplements within 7 days or 5 half-lives of the respective drug, if known (whichever is longer), prior to dosing.
• •Patients with Epilepsy (Stage II (Phase 1b)):
• •3. Acute precipitant of seizure within the past 3 months prior to screening such as major trauma, hypoglycemia, hyperglycemia, cardiac arrest, or post-anoxia
• •All Subjects:
• •4. Any uncontrolled medical or psychiatric condition (e.g., hypertension, diabetes, chronic obstructive pulmonary disorder, asthma, depression) as judged by the investigator.
• •5. Any clinically significant findings in medical examination, including physical examination, 12-lead ECG, vital signs, clinical laboratory tests. Specifically:
• •1. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN), Total bilirubin ≥ 2 × ULN
• •2. QT interval corrected by Fridericia's formula (QTcF) \> 450 msec (male) or \> 470 msec (female)
• •6. Undergone major surgery ≤ 2 months prior to Day -1.
• •7. Received any investigational drug within 30 days or 5 half-lives (whichever is longer, if known) before screening.
• •8. Received any vaccine within 6 weeks before planned SIF001 administration.
• •9. Loss of more than 100 mL blood (e.g., a blood donation) within 2 months before Day -1, or has received any blood, plasma, or platelet transfusions within 3 months before admission.
• •10. Active liver disease or severe renal impairment, including serum creatinine ≥ 1.5 × ULN or estimated glomerular filtration rate of \< 60 mL/min/1.73m2.
• •11. Known history of substance use disorder.
• •12. History of active human immunodeficiency virus (HIV), active hepatitis C virus (HCV), or active hepatitis B virus (HBV)
• •13. Recent (2 weeks) history of a positive COVID-19 test result or disease symptoms of COVID-19 disease such as shortness of breath, cough, rhinorrhea, sore throat etc.
• •14. Known history of hypersensitivity or anaphylactic reaction to intravenous medications, biologicals, or fluids.
• •15. History of any clinically significant disease or disorder which, in the opinion of the investigators, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• •16. History of status epilepticus within 2 years of screening
• •17. Known history of suicidality within 2 years of screening, or answering "yes" to questions 4 and 5 of the Columbia Suicide Severity Rating Scale (C-SSRS)
• •18. Unable to complete this study for other reasons or the investigator believes that the subject should be excluded.