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Evaluation of the Food Effect on the Safety, Tolerability, PK of EC-18 After Oral Administration in Healthy Volunteers

Phase 1
Completed
Conditions
Chemotherapy-Induced Neutropenia
Interventions
Dietary Supplement: high-fat diet
Registration Number
NCT02700360
Lead Sponsor
Enzychem Lifesciences Corporation
Brief Summary

A Randomized, Open-Label, Single -Dose, Crossover, Phase I Clinical Trial to Evaluate the Effect of Food on the Safety, Tolerability and Pharmacokinetics of EC-18 after Oral Administration in Healthy Volunteers

Detailed Description

In vitro and in vivo efficacy studies and clinical trials have shown that EC-18 has a mode of action of improving neutropenia by promoting neutrophil production from hematopoietic stem cells and at the same time, efficiently controlling STAT6/Complement 3(C 3), suggesting its potential to be developed as an orally administered new drug for treatment of neutropenia resulting from decreased neutrophils caused by administration of an anticancer agent.

This study is a randomized, open-Label, single -dose, crossover, phase I clinical trial to evaluate the effect of food on the safety, tolerability and pharmacokinetics of EC-18 after oral administration in healthy volunteers

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
Inclusion Criteria
  1. Healthy adult aged between 19 and 45 years, inclusive, at the time of providing the informed consent form

  2. body weight: ≥ 55kg(male), ≥ 50kg(female)

  3. BMI: 18.5 kg/m2 ≦ BMI < 25.0 kg/m2 [BMI(body mass index) = Body weight (kg)/[height (m)]2 ]

  4. in female subjects, the result of serum β-hCG pregnancy test comes out negative at screening, urine β-hCG test comes out negative before taking medication during the period set by this protocol have to be included one of the below conditions.

    • postmenopausal(no natural menstruation at least 2 years)

    • surgically sterile(hysterectomy or bilateral ovariotomy, tubal ligation or sterile condition by other ways)

    • sterility of male partner before screening(proof the azoospermia after vasectomy), and this is the only partner of the subject.

    • agree with using a proper and continuous method of contraception start on 14 days(at least) before the1st IND administration and for 28 days(at least) after the last IND administration

      • proper contraception means physical barrier method including condom, contraceptive diaphragm or cervix cap, do not use a hormones including contraceptive or oral contraceptive during the study.
  5. if the male have a sex life with childbearing aged female, maintain proper contraception during the study and for 28 days after the last IND administration, agree with "do not donate the sperm"(if the female partner is infertility, above contraceptions are not necessary)

  6. Written consent on voluntary decision of participation and compliance with precautions after being fully informed of and completely understanding this trial

Exclusion Criteria
  1. Hypersensitivity to a drug containing an ingredient of the investigational product(EC-18) or similar ingredient (e.g., deer antler) or other drugs (e.g., aspirin, antibiotics) or medical history of clinically significant hypersensitivity
  2. Active infection such as chronic or local infection based on screening tests or inquiry, verifiable medical records
  3. Serious infection that required hospitalization or use of antibiotics within 30 days prior to the first dose of the investigational product, based on an inquiry or verifiable medical records
  4. Presence of a clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrine, nervous, blood, cardiovascular, urogenital, psychiatric disorder or its prior history
  5. (1) Presenting tuberculosis or prior history of tuberculosis or (2) positive results from a QuantiFERON®-TB Gold in Tube Assay conducted due to a contact with a tuberculosis patient within the past 3 months or signs and symptoms of suspected tuberculosis
  6. Prior history of a gastrointestinal disorder (e.g., Crohn's disease, ulcer) or surgery (except for simple appendectomy or hernia surgery) that may affect drug absorption, etc.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Part 1(1,000mg dose): group 2high-fat dietperiod 1: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, on an empty stomach; period 2: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, after high-fat diet intake; cross-over period: 7 days
Part 2(500mg dose): group 3high-fat dietperiod 1: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, after high-fat diet intake; period 2: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, on an empty stomach; cross-over period: 7 days
Part 2(500mg dose): group 4high-fat dietperiod 1: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, on an empty stomach; period 2: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, after high-fat diet intake; cross-over period: 7 days
Part 1(1,000mg dose): group 1high-fat dietperiod 1: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, after high-fat diet intake; period 2: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, on an empty stomach; cross-over period: 7 days
Part 2(2,000mg dose): group 5high-fat dietperiod 1: EC-18 2,000 mg(500 mg/cap, 4 capsules) once daily, after high-fat diet intake; period 2: EC-18 2,000 mg(500 mg/cap, 4 capsules) once daily, on an empty stomach; cross-over period: 7 days
Part 2(2,000mg dose): group 6high-fat dietperiod 1: EC-18 2,000 mg(500 mg/cap, 4 capsules) once daily, on an empty stomach; period 2: EC-18 2,000 mg(500 mg/cap, 4 capsule) once daily, after high-fat diet intake; cross-over period: 7 days
Part 1(1,000mg dose): group 1EC-18period 1: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, after high-fat diet intake; period 2: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, on an empty stomach; cross-over period: 7 days
Part 1(1,000mg dose): group 2EC-18period 1: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, on an empty stomach; period 2: EC-18 1,000 mg(500 mg/cap, 2 capsules) once daily, after high-fat diet intake; cross-over period: 7 days
Part 2(500mg dose): group 3EC-18period 1: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, after high-fat diet intake; period 2: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, on an empty stomach; cross-over period: 7 days
Part 2(500mg dose): group 4EC-18period 1: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, on an empty stomach; period 2: EC-18 500 mg(500 mg/cap, 1 capsule) once daily, after high-fat diet intake; cross-over period: 7 days
Part 2(2,000mg dose): group 5EC-18period 1: EC-18 2,000 mg(500 mg/cap, 4 capsules) once daily, after high-fat diet intake; period 2: EC-18 2,000 mg(500 mg/cap, 4 capsules) once daily, on an empty stomach; cross-over period: 7 days
Part 2(2,000mg dose): group 6EC-18period 1: EC-18 2,000 mg(500 mg/cap, 4 capsules) once daily, on an empty stomach; period 2: EC-18 2,000 mg(500 mg/cap, 4 capsule) once daily, after high-fat diet intake; cross-over period: 7 days
Primary Outcome Measures
NameTimeMethod
evaluate safety and tolerability: physical examination(change value from baseline)screening, Day-3(Day5), Day3(Day10) and Day15(follow-up)
evaluate safety and tolerability: EKG(change value from baseline)screening, Day-3(Day5) and Day15(follow-up)
evaluate safety and tolerability: Number and severity of ADRs monitoring such as subjective, objective symptom(change value from baseline)Day-3(Day5), Day-2(Day6), Day-1(Day7), Day1(Day8), Day2(Day9), D3(Day10) and Day15(follow-up)
evaluate safety and tolerability: clinical laboratory test(change value from baseline)screening, Day-3(Day5), Day3(Day10) and Day15(follow-up)
evaluate safety and tolerability:vital sign(change value from baseline)screening, 0(before medication) of Day-3(Day5), Day-2(Day6), Day-1(Day7), Day1(Day8), after medication 4, 12, 24, 36, 48hours and Day15(Follow-up)
Secondary Outcome Measures
NameTimeMethod
evaluate pharmacokinetics: Cmax33 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours
evaluate pharmacokinetics: AUClas33 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours
evaluate pharmacokinetics: tmax33 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours
evaluate pharmacokinetics: AUCinf33 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours
evaluate pharmacokinetics: t1/233 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours
evaluate pharmacokinetics: Vd/F33 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours
evaluate pharmacokinetics: CL/F33 times per each period, total 66 times; Day-2(Day6):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours; Day1(Day8):0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48hours

Trial Locations

Locations (1)

Yonsei University Health System, Severance Hospital

🇰🇷

Seoul, Korea, Republic of

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