Study of Safety and Pharmacokinetics of Oral Doses of EPX-100 in Healthy Subjects.

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Brief Title

Study of Safety and Pharmacokinetics of Oral Doses of EPX-100 in Healthy Subjects.

Official Title

A Phase I, Placebo-Controlled, Double-Blind, 2-Period Study to Assess Safety and Pharmacokinetics of Escalating Single and Multiple Oral Doses of EPX-100 in Fasting Healthy Subjects and Following a High-Fat Meal

Brief 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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Treatment-emergent adverse events (TEAEs)

Secondary Outcome

 Plasma Concentrations of EPX-100 in Fasting State

Condition

Dravet Syndrome

Intervention

EPX-100 (Clemizole Hydrochloride)

Study Arms / Comparison Groups

 EPX-100
Description:  Single and multiple doses of 20, 40, 80mg of EPX-100 (Clemizole Hydrochloride)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

24

Start Date

August 29, 2019

Completion Date

November 27, 2019

Primary Completion Date

November 27, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent prior to any study-related procedures

          2. Male or female subjects 18 to 50 years of age inclusive

          3. Subject's body mass index (BMI) is ≤ 30 kg/m2

          4. Female subjects of childbearing potential must not be pregnant or lactating with a
             negative serum human chorionic gonadotropin (HCG) pregnancy test result at Screening,
             Day -1, or Day 19.

          5. Female subjects of childbearing potential and male subjects must use an adequate
             method of contraception from Screening until completion of the study. Acceptable
             methods of contraception are barrier methods (male condom, female condom, diaphragm,
             cervical cap, spermicide, or intrauterine device [IUD]), surgical sterility
             (documented doctor's report of vasectomy, hysterectomy, and/or bilateral
             oophorectomy), oral hormonal contraceptives, hormonal IUD, and/or postmenopausal
             status (defined as at least 1 year without menses as demonstrated by medical history
             or subject report).

          6. Subject is in good health as determined by vital signs, medical history, physical
             exam, and safety laboratory analyses at Screening and during the study.

        Exclusion Criteria:

          1. Subject has used an investigational product within 30 days prior to enrollment or
             during the study.

          2. Subject has used prescription or non-prescription drugs (including vitamins, minerals,
             and herbal/plant-derived preparations) within 2 weeks of enrollment (excluding oral
             hormonal contraceptives, hormonal IUD, hormone replacement therapy, and acetaminophen)
             unless deemed acceptable by the Investigator in consultation with the Sponsor.

          3. Subject has a positive drug and/or alcohol test at Screening, Day -1, or Day 19.

          4. Subject has a history of drug or alcohol abuse within 2 years before Screening.

          5. Subject is unable to abstain from ingesting alcohol, caffeine, grapefruit or
             grapefruit juice, pomelo or pomelo juice, or Seville oranges or Seville orange juice
             for 72 hours prior to dosing and throughout the dosing periods.

          6. Concurrent use of substances, including drugs, known to interfere with EPX-100,
             including moderate or severe inducers or inhibitors of CYP3A4 and CYP2D6.

          7. The subject has a clinically significant history of endocrinologic, hematologic,
             hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic,
             psychiatric, renal, and/or other major diseases or malignancy.

          8. Subject has evidence of any of the following cardiac conduction abnormalities:

               1. QTcF interval >430 msec for males and >450 msec for females

               2. PR interval ⩾ 200 msec

               3. Evidence of second- or third-degree atrioventricular block (AVB)

               4. Electrocardiographic evidence of complete left bundle branch block (LBBB),
                  complete right bundle branch block (RBBB), or incomplete LBBB

               5. Intraventricular conduction delay with QRS duration >120 msec

               6. Heart rate <40 bpm

               7. Pathological Q waves (defined as >40 msec or depth >0.4-0.5 mV)

               8. Evidence of ventricular pre-excitation.
      

Gender

All

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Hahn-Jun Lee, Ph.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04069689

Organization ID

EPX-100-002


Responsible Party

Sponsor

Study Sponsor

Epygenix


Study Sponsor

Hahn-Jun Lee, Ph.D., Study Director, Epygenix Therapeutics, Inc.


Verification Date

June 2020