Study to Evaluate Efficacy and Safety of Entelon 50mg in Patients With Non-Proliferative Diabetic Retinopathy

Study Overview
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Brief Summary
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This clinical trial is a multi-center, double-blind, randomized, placebo controlled , parallel design, superiority, phase 4 study to evaluate the efficacy and safety of Entelon 50mg in 396 patients with non-proliferative diabetic retinopathy.

Detailed Description
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This study is to prove that Entelon tab. 50mg is superior in clinical efficacy and safety compared to placebo for 24 months in patients suffering from non-proliferative diabetic retinopathy.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled, Superiority, Phase IV Trial to Evaluate the Efficacy and Safety of Entelon 50mg Compared to Placebo in Patients With Non-Proliferative Diabetic Retinopathy

Conditions
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Non Proliferative Diabetic Retinopathy

Intervention / Treatment
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* Drug: Entelon Tab. 50mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 19 years ≤ age Those who are diagnosed as Type 2 diabetes mellitus Those whose blood sugar level has been well adjusted to less than 9% of HbA1c with dietary and oral blood sugar lowering durgs for 3 months based on the time of screening Those who agree to use an effective method of contraception Those who provide written consent voluntarily to participate in this clinical trial Inclusion criteria for the study eye Those with 0.5(20/40 Snellen lines) or more visual acuity Those with 300 micrometers or less central macular thickness Those who are diagnosed as mild to moderate NPDR(DRSS levels 35-47) Exclusion Criteria: Those who are diagnosed as proliferative diabetic retinopathy Those with macular edema Diabetic subjects who have difficulty in controlling blood sugar Those whose blood pressure is not well controlled at the time of the screening(>140/90mmHg) Those who, have had stroke or myocardial infarction or arrhythmia that should be treated within 6 months prior to the time of screening Subjects with severe renal disorder or severe liver disorder Those who have a history of malignant tumors within 5 years prior to the time of screening Those who are required to receive Kallidinogenase, Vaccinium myrtillus extract, Sulodexide, or Calcium dobesilate during the clinical trial period Those who have an allergy to investigational product or any of its excipients Those who have an allergy to fluorescein Those who have galactose intolerance, lapp lactase deficiency, or glucose-galactose malabsorption Those who have difficulty to get OCT test or Fundus photo test Pregnant or lactating woman Those with medication of other investigational product within 3 months prior to the time of randomization Patients who are considered to be ineligible for study participation by the investigator Exclusion criteria for the study eye Those who have a visual defect that can affect the evaluation determined by an investigator Those who have a opacity that can affect the evaluation determined by an investigator Those who have eye diseases that can affect the evaluation determined by an investigator Those with 25mmHg or more intraocular pressure on a study eye Those who are on medication of intravitreal injection of steroid or anti VEGF treatment or get laser photocoagulation within 6 months prior to the first administration Those who have a history of a vitrectomy Those who have a major ophthalmic surgery history within 3 months prior to the time of first administration for investigational products Those who have a history of yttrium aluminum garnet capsulotomy within 2 months prior to the time of first administration for investigational products Those with a phakia

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entelon Tab. 50mg<br> | Drug: Entelon Tab. 50mg<br>* twice daily for 24months<br>* Other names: Vitis Vinifera Seed Dreid Extract 50mg;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* twice daily for 24months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects maintained or improved in DRSS level | Change at 24 months of treatment with the drug from baseline(day 0) in DRSS(Diabetic Retinopathy Severity Scale) level | 24 months(Visit 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects maintained or improved in DRSS level | Change at 12 months of treatment with the drug from baseline(day 0) in DRSS(Diabetic Retinopathy Severity Scale) level | 12 months(Visit 6) | 
| Proportion of subjects maintained or improved or worsened in DRSS | Percentage of subjects with no change in DRSS(diabetic retinopathy severity scale) compared to baseline at 12 or 24 months compared to baseline, improved one or more levels, improved two or more levels, worsened one or more levels, and worsened two or more levels | 12 months(Visit 6), 24 months(Visit 10) | 
| Amount of change BCVA letter | Amount of change in BCVA(best corrected visual acuity) letters at 24 months relative to baseline | 24 months(Visit 10) | 
| Proportion of subjects improved or worsened in BCVA | Proportion of subjects with improved five or more letters in BCVA(best corrected visual acuity) and worsened five or more letters at 24 months compared to baseline | 24 months(Visit 10) | 
| Change in quantitative of hard exudate | Amount and rate of change in quantitative of hard exudate through fundus photo | 6 months(Visit 4), 12 months(Visit 6), 18 months(Visit 8), 24 months(Visit 10) | 
| Change in CMT and TMV | Amount of change in CMT(Central macular thickness) and TMV(Total macular volume) | 6 month(Visit 4), 12 month(Visit 6), 18 month(Visit 8), 24 month(Visit 10) | 
| Proportion of subjects with CSME | Proportion of subjects with CSME(Clinically significant macular edema) | through study completion, an average of 2 years |