Clinical trial NCT02532712: Study to Evaluate the Safety, Tolerability and PK of EC-18 After Oral Administration in Healthy Volunteers
Official title: A Dose Block-randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Escalation, Phase I Clinical Trial to Evaluate the Safety, Tolerability and PK of EC-18 After Oral Administration in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chemotherapy-Induced Neutropenia
Keywords: EC-18
Hematology
Cancer
Neutropenia
Lead sponsor: Enzychem Lifesciences Corporation
Sponsor class: INDUSTRY
First posted: 2015-08-26
Enrollment: 64
Sex: MALE
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a Dose block-randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Escalation, Phase I clinical trial to assess the safety, tolerability and pharmacokinetics of single-dose and multiple-dose oral administration of the investigational product, EC-18 (study drug) in healthy adult male 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(C3), 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 Dose block-randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Escalation, Phase I clinical trial to assess the safety, tolerability and pharmacokinetics of single-dose and multiple-dose oral administration of the investigational product, EC-18 (study drug) in healthy adult male volunteers.

Eligibility criteria: Inclusion Criteria:

* Healthy adult male aged between 19 and 45 years, inclusive, at the time of providing the informed consent form
* Body weight ≥ 50 kg, and calculated BMI in the range of 18.5 kg/m2 ≤ BMI \< 25.0 kg/m2 ☞ BMI(body mass index) = Body weight (kg)/\[height (m)\]2
* No inherited or chronic disease and pathologic symptoms or findings from internal examinations
* Eligible subject based on findings from clinical laboratory tests, such as hematology, blood chemistry, urinalysis and immunoserology, and ECG, as conducted by a responsible doctor depending on characteristics of the drug
* Written consent on voluntary decision of participation and compliance with precautions after being fully informed of and completely understanding this trial
* Consent to practice medically acceptable contraception during the trial

Exclusion Criteria:

* 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
* Active infection such as chronic or local infection based on screening tests or inquiry, verifiable medical records
* 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
* Presence of a clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrine, nervous, blood, cardiovascular, urogenital, psychiatric disorder or its prior history
* (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
* 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.

Primary outcomes:
measure: No. and severity of Adverse event as a Measure of Safety and Tolerability
timeFrame: From date of D-1 until Follow-up visit: up to 30 days
measure: Vital signs, physical examination, clinical laboratory tests, ECG as a Measure of Safety and Tolerability
timeFrame: From date of screening until Follow-up visit: up to 60 days
Secondary outcomes:
measure: Pharmacokinetic parameters of EC-18 following single oral dose: Cmax (Maximum observed plasma drug concentration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following single oral dose: Tmax (Time of maximum drug concentration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following single oral dose: AUClast (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following single oral dose: AUCinf (Area under the plasma concentration-time curve from time zero extrapolated to the infinite time)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following single oral dose: t1/2 (Half-life)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following single oral dose: CL/F (Apparent total clearance of the drug from plasma after oral administration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Cmax,ss (Maximum (peak) steady-state plasma drug concentration during a dosage interval)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Cmin,ss (Minimum steady-state plasma drug concentration during a dosage interval)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Cavg,ss (Average steady-state plasma drug concentration during multiple-dose administration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Fluctuation
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: t1/2 (half-life)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: AUCτ (Area under the plasma concentration-time curve from time zero to time t)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: AUCinf (Area under the plasma concentration-time curve from time zero to infinity)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Cmax (Maximum (peak) plasma drug concentration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Tmax (Time to reach maximum (peak) plasma concentration following drug
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: CL/F (Apparent total clearance of the drug from plasma after oral administration)
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
measure: Pharmacokinetic parameters of EC-18 following multiple oral doses: Accumulation index
timeFrame: [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
affiliation: Yonsei University Health System, Severance Hospital (Seoul)
name: Min-Soo Park, Professor
role: PRINCIPAL_INVESTIGATOR
References: