Study to Evaluate the Safety, Tolerability and PK of EC-18 After Oral Administration in Healthy Volunteers

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chemotherapy-Induced Neutropenia

Intervention / Treatment
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* Drug: EC-18
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose group-Group 1-Experimental<br>Single dose, 500mg of Study drug(EC-18) | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Single dose group-Group 1-Placebo<br>Single dose, 500mg of Placebo | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Single dose group-Group 2-Experimental<br>Single dose, 1000mg of Study drug(EC-18) | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Single dose group-Group 2-Placebo<br>Single dose, 1000mg of Placebo | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Single dose group-Group 3-Experimental<br>Single dose, 2000mg of Study drug (EC-18) | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Single dose group-Group 3-Placebo<br>Single dose, 2000mg of Placebo | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Single dose group-Group 4-Experimental<br>Single dose, 4000mg of Study drug (EC-18) | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Single dose group-Group 4-Placebo<br>Single dose, 4000mg of Placebo | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Multiple dose group-Group 1-Experimental<br>Multiple dose, Study drug(EC-18) 500mg, Once daily, for 14 days | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Multiple dose group-Group 1-Placebo<br>Multiple dose, Placebo 500mg, Once daily, for 14 days | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Multiple dose group-Group 2-Experimental<br>Multiple dose, Study drug(EC-18) 1000mg, Once daily, for 14 days | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Multiple dose group-Group 2-Placebo<br>Multiple dose, Placebo 1000mg, Once daily, for 14 days | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Multiple dose group-Group 3-Experimental<br>Multiple dose, Study drug(EC-18) 2000mg, Once daily, for 14 days | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Multiple dose group-Group 3-Placebo<br>Multiple dose, Placebo 2000mg, Once daily, for 14 days | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|
| Experimental: Multiple dose group-Group 4-Experimental<br>Multiple dose, Study drug(EC-18) 4000mg, Once daily, for 14 days | Drug: EC-18<br>* EC-18 Soft-capsule (500mg/1 capsule)<br>* Other names: EC18 Soft-capsule;|
| Placebo Comparator: Multiple dose group-Group 4-Placebo<br>Multiple dose, Placebo 4000mg, Once daily, for 14 days | Drug: Placebo<br>* Placebo with same shape and size<br>* Other names: Placebo for EC-18 (Sofe-capsule);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No. and severity of Adverse event as a Measure of Safety and Tolerability |  | From date of D-1 until Follow-up visit: up to 30 days | 
| Vital signs, physical examination, clinical laboratory tests, ECG as a Measure of Safety and Tolerability |  | From date of screening until Follow-up visit: up to 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of EC-18 following single oral dose: Cmax (Maximum observed plasma drug concentration) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following single oral dose: Tmax (Time of maximum drug concentration) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose | 
| 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) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose | 
| 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) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following single oral dose: t1/2 (Half-life) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following single oral dose: CL/F (Apparent total clearance of the drug from plasma after oral administration) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Cmax,ss (Maximum (peak) steady-state plasma drug concentration during a dosage interval) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Cmin,ss (Minimum steady-state plasma drug concentration during a dosage interval) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Cavg,ss (Average steady-state plasma drug concentration during multiple-dose administration) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Fluctuation |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: t1/2 (half-life) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: AUCτ (Area under the plasma concentration-time curve from time zero to time t) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: AUCinf (Area under the plasma concentration-time curve from time zero to infinity) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Cmax (Maximum (peak) plasma drug concentration) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Tmax (Time to reach maximum (peak) plasma concentration following drug |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: CL/F (Apparent total clearance of the drug from plasma after oral administration) |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 
| Pharmacokinetic parameters of EC-18 following multiple oral doses: Accumulation index |  | [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 16, 24, 36, 48 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EC-18, Hematology, Cancer, Neutropenia