Phase 4 Study to Evaluate Efficacy and Safety of Entelon Tab.150mg in Patients With Chronic Venous Disease(CVD)

Study Overview
=================
Brief Summary
-----------------
This clinical trial is a multi-center, double-blind, randomized, active controlled , parallel design, non-inferiority phase 4 study to evaluate the efficacy and safety of Entelon 150mg in 278 patients with chronic venous disease.

Detailed Description
-----------------
This study is to prove that Entelon tab. 150mg is non-inferior in clinical efficacy and safety compared to Venitol tab. for 8 weeks in patients suffering from chronic venous disease.

Official Title
-----------------
A Multicenter, Double-blind, Randomized, Active Controlled, Parallel Group, Non-inferiority Phase 4 Study to Evaluate Efficacy and Safety of Entelon Tab.150mg in Patients With Chronic Venous Disease(CVD)

Conditions
-----------------
Chronic Venous Disease

Intervention / Treatment
-----------------
* Drug: Entelon Tab.150mg
* Drug: Venitol Tab.
* Drug: Placebo of Venitol Tab.
* Drug: Placebo of Entelon Tab.150mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 19 years ≤ age ≤ 80 years Those who are diagnosed as CEAP Classification Class 1   Class 3 Those who have the Venous Duplex ultrasonography result at least one of the following reflux more than 1 second in Femoral vein or Popliteal vein reflux more that 0.5 second in GSV or SSV or Accessory saphenous vein or perforating vein or calf vein Those who have completed the washout period as following until the baseline, including the screening period Analgesic, corticosteroids, anti-inflammatory drugs: at least 2 weeks Those who provide written consent voluntarily to participate in this clinical trial Exclusion Criteria: Those who must wear compression stockings Those who have obstruction of the peripheral arteries of the lower extremities Those who have asymptomatic varicose veins Those who have acute deep vein thrombosis Those who have frequent lower extremity pain due to neuropathy Varicose vein surgery patient or prospective person (if surgery was done more than 1 year prior to the time of screening, recruitment is possible) Those who have systemic disease that causes edema or thrombosis Those who have a history of malignant tumors within 5 years prior to the time of screening Those who have severe renal dysfunction at the time of screening (serum creatinine ≥ 2 x upper limit of normal) Those who have severe liver dysfunction at the time of screening (AST or ALT ≥ 3 x upper limit of normal) Those who are required to receive diuretics, analgesics, corticosteroids, anti-inflammatory drugs, or contraindications that may affect the outcome of this clinical trial during the clinical trial period Those who have a history of significant mental illness, alcohol abuse Patients who have an allergy to investigational product or any of its excipients Patients who participated in other clinical trials within 12 weeks prior to the date of screening Pregnant or lactating woman Those who do not agree to use an effective method of contraception Individual considered by the investigator to be ineligible for study participation

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entelon Tab.150mg<br> | Drug: Entelon Tab.150mg<br>* twice daily for 8 weeks<br>* Other names: Vitis Vinifera Seed Dreid Extract 150mg;Drug: Placebo of Venitol Tab.<br>* twice daily for 8 weeks (with Entelon Tab.150mg. It is for the masking.)<br>|
| Active Comparator: Venitol tab.<br> | Drug: Venitol Tab.<br>* twice daily for 8 weeks<br>* Other names: Purified and Micronized Flavonoid Fraction 500mg;Drug: Placebo of Entelon Tab.150mg<br>* twice daily for 8 weeks(with Venitol Tab. It is for the masking.)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CIVIQ-20 questionnaire score change | Change at week 8 of treatment with the drug from baseline(day 0) in CIVIQ-20 questionnaire score | 8week(Visit 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CIVIQ-20 questionnaire score change | Change at week 4 of treatment with the drug from baseline(day 0) in CIVIQ-20 questionnaire score | 4week(Visit 3) | 
| AVVQ questionnaire score change | Change at week 4, 8 of treatment with the drug from baseline(day 0) in AVVQ questionnaire score | 4week(Visit 3), 8week(Visit 4) | 
| 100mm VAS score change of leg heaviness, leg pain, leg cramps | Change at week 4, 8 of treatment with the drug from baseline(day 0) in symptoms of leg heaviness, leg pain, leg cramps thorugh 100mm VAS score | 4week(Visit 3), 8week(Visit 4) | 
| Venous clinical severity score change | change at week 4, 8 of treatment with the drug from baseline(day 0) in Venous clinical severity score | 4week(Visit 3), 8week(Visit 4) | 
| change in the circumference of the leg due to edema | change at week 8 of treatment with the drug from baseline(day 0) in leg circumference | 8week(Visit 4) |