Study of Safety and Pharmacokinetics of Oral Doses of EPX-100 in Healthy Subjects.
Condition: Dravet Syndrome
MeSH terms: Epilepsies, Myoclonic
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a placebo-controlled, double-blind, 2-period study in 3 sequential groups of 8
      healthy subjects each. The safety and pharmacokinetics of escalating single and multiple oral
      doses of EPX-100 will be assessed in fasting healthy subjects and following a high-fat meal.
    

Detailed description: 
      This is a placebo-controlled, double-blind, 2-period study in 3 sequential groups of 8
      healthy subjects each. Subjects will be admitted on two occasions to the clinical research
      center: Day -1 for 14 days and discharged on Day 13 and then re-admitted on Day 19 for 3 days
      and discharged on Day 21. Subjects will fast after midnight on the day of each admission.

      On Day 1 of study of the low-dose group (cohort 1), subjects will be randomized to a single
      dose of 20 mg EPX-100 (N=6) or placebo (N=2) in the morning and then remain fasting for 4
      hours after dosing. Safety will be assessed and blood samples will be obtained to calculate
      PK at the following time points: 0, 0.5, 1, 2, 4, 6, 8, 12, 18, and 24 hours following the
      first dose of EPX-100 or placebo. The subjects will remain in the study research center for
      daily 8 AM (± 2 hours) blood samples for 5 consecutive days (Days 3 - 7; one blood sample per
      day). On Days 8 - 11, subjects will be administered 20 mg EPX-100 or placebo twice daily
      (BID) at least one hour prior to the morning meal and at least 2 hours after the evening meal
      (approximately 12 hours apart). A single dose of 20 mg EPX-100 or placebo will be
      administered on Day 12 in the fasting state and subjects will remain fasting for 4 hours
      after dosing. Blood samples will be drawn at the following time points: 0, 0.5, 1, 2, 4, 6,
      8, 12, 18, and 24 hours to determine multiple-dose PK. After a washout period of at least one
      week following the last dose of EPX-100 or placebo, subjects will return to the clinical
      research center on Day 19 and safety will be assessed. On Day 20, subjects will ingest a
      high-fat morning meal over 30 minutes; thereafter, the subject will receive a single dose of
      20 mg EPX- 100 or placebo at 30 minutes after the start of the meal. Blood samples will be
      drawn at the following time points: 0, 0.5, 1, 2, 4, 6, 8, 12, 18, and 24 hours after the
      administration of study drug to determine the PK of EPX-100 in the fed state. Once the 20 mg
      dose level of EPX-100 is evaluated and the Safety Review Committee (SRC) determines it is
      safe to escalate to the next dose level, subsequent groups of 8 subjects each will be
      administered 40 mg (cohort 2) and 80 mg (cohort 3) (N=6 active drug, N=2 matching placebo)
      EPX-100 and follow the same study procedures as the low-dose group (cohort 1).

      Throughout the study period, subjects will undergo cardiac assessments, safety assessments,
      and PK sampling.
    

Intervention name(s): EPX-100 (Clemizole Hydrochloride); Placebos
Intervention type(s): Drug; Drug
Intervention description(s): EPX-100 (Clemizole Hydrochloride); Placebo to match EPX-100
Other intervention name(s): Clemizole Hydrochloride; Clemizole HCL
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Clemizole