Efficacy and Safety Study of Probucol in Patients With Diabetic Nephropathy

Study Overview
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Brief Summary
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This trial is randomized, placebo-controlled, double blind, double dummy, multi-centre trial. Screening period (4 week) Double blind treatment period (16 weeks)

Detailed Description
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Usage: 16 week, BID, Prescribed Oral with the breakfast and dinner Dosage:Placebo group: placebo 2 tablets, 16 weeks Probucol 250mg group: probucol 125mg 2 tablets, 16 weeks Probucol 500mg group: probucol 250 mg 2 tablets, 16 weeks

Official Title
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A Phase II, Multicenter, Randomized, Double Blind, Double-dummy, 16-week, Placebo Controlled Study to Evaluate the Efficacy and Safety of Probucol in Patients With Nephropathy Due to Type 2 Diabetes.

Conditions
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Diabetic Nephropathy

Intervention / Treatment
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* Drug: Probucol 250mg/day
* Drug: Probucol 500mg/day
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is male or female diagnosed with type 2 diabetes mellitus and must be aged 20 to 75 years at the time of screening visit Urinary albumin excretion > 300 mg/g Cr at screening visit Subjects administered ACEI or ARB without changing dosage prior to 3 months at the screening visit (if subjects administered ACEI or ARB) Subjects administered statins without changing dosage prior to 3 months at the screening visit(if subjects administered statins) or subjects have no plan to administered to statin(if subjects is not administered statin) 15 mL/min ≤ eGFR ≤ 90 mL min Subjects must be willing and able to give signed and dated written informed consent. Exclusion Criteria: Type 1 DM or gestational diabetes Subjects on Renal replacement therapy or Renal transplantation prior to Screening visit Ventricular arrhythmia (multiple and multifocal premature ventricular contractions) Cardiac damage (abnormally levels of Troponin I) Subject with medical history of cardiac syncope or primary syncope Has condition that may prolong QTc interval (for man QTc interval>450msec, for woman QTc interval>470msec) at screening Pregnant or lactating woman before randomization Inflammatory bowel disease (ulcerative colitis, Crohn's disease) Cholestasis Congestive heart failure Subjects with a myocardial infarction, Unstable angina, or cerebral infarction within the latest 6 months Subjects has a diagnosis of NYHA grade III-IV status AST or ALT is 3.0 times higher than the upper limit of the normal range Active hepatitis Or Liver cirrhosis Subjects with Hyperkalemia (K>5.5 mEq/L) Subjects with Renal Artery stenosis Subjects with Malignancy within the 5 years at the time of screening visit(except for treated Basal cells carcinoma or squamous cell carcinoma) Urinary tract disease (urinary tract infection, Neurogenic bladder) Kidney disease (nephritis, chronic glomerulonephritis or polycystic kidney disease) Has an allergic history to probucol HbA1c > 9% Systolic blood pressure ≥ 160 mmHg or Diastolic blood pressure ≥ 100 mmHg Subjects taken probucol within 3 months prior to Screening The subject has received an investigational product or biological agent within 3 months prior to screening Subjects otherwise judged by the investigator or sub investigator to be inappropriate for inclusion in the trial

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Probucol 250mg/day<br>Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks | Drug: Probucol 250mg/day<br>* Probucol 250mg + Placebo<br>* Other names: Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks;|
| Experimental: Probucol 500mg/day<br>Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks | Drug: Probucol 500mg/day<br>* Probucol 500mg + Placebo<br>* Other names: Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks;|
| Placebo Comparator: Placebo<br>Placebo group: placebo 2 tablets, 16 weeks | Drug: Placebo<br>* Probucol matching placebo<br>* Other names: placebo 2 tablets, 16 weeks;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A/C ratio | The change in the A/C ratio from baseline to the end of treatment(16 week) [Time Frame: baseline to 16 weeks] | 16 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatinine | The change in the Serum creatinine from baseline to the end of treatment. | 16 week | 
| eGFR | The change in the eGFR from baseline to the end of treatment(16 week) | 16 week | 
| cystatin C | The change in the cystatin C from baseline to the end of treatment(16 week) | 16 week | 
| urine albumin | The change in the urine albumin from baseline to the end of treatment(16 week) | 16 week | 
| P/C ratio | The change in the P/C ratio from baseline to the end of treatment(16 week) | 16 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic nephropathy, Albumin creatinine ratio, Probucol