Efficacy and Safety Study of Probucol in Patients With Diabetic Nephropathy

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.

This trial is randomized, placebo-controlled, double blind, double dummy, multi-centre trial.

• Screening period (4 week)
• Double blind treatment period (16 weeks)

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Drug: Probucol 250mg/day; Drug: Probucol 500mg/day; Drug: Placebo

Detailed Description

1. Usage: 16 week, BID, Prescribed Oral with the breakfast and dinner
2. 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

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of
    • The Catholic University of Korea, Bucheon St. Mary's Hospital
  • DaeGu, Korea, Republic of
    • Kyungpook National University
  • DaeGu, Korea, Republic of
    • Yeungnam University Medical Center
  • InCheon, Korea, Republic of
    • Inha University Hospital
  • Incheon, Korea, Republic of
    • Gil Hospital
  • JeonJu, Korea, Republic of
    • Chonbuk National University Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Eulji Hospital
  • Seoul, Korea, Republic of
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of
    • Kangnam Sacred Hospital
  • Seoul, Korea, Republic of
    • Kyunghee Univ Hospital at Kangdong
  • Seoul, Korea, Republic of
    • Samsumg Medical Center
  • SungNam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Suwon, Korea, Republic of
    • St. Vincent Hospital
  • Uijeongbu, Korea, Republic of
    • Uijeongbu St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Urinary albumin excretion > 300 mg/g Cr at screening visit
3. Subjects administered ACEI or ARB without changing dosage prior to 3 months at the screening visit (if subjects administered ACEI or ARB)
4. 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)
5. 15 mL/min ≤ eGFR ≤ 90 mL min
6. Subjects must be willing and able to give signed and dated written informed consent.

Exclusion Criteria:

1. Type 1 DM or gestational diabetes
2. Subjects on Renal replacement therapy or Renal transplantation prior to Screening visit
3. Ventricular arrhythmia (multiple and multifocal premature ventricular contractions)
4. Cardiac damage (abnormally levels of Troponin I)
5. Subject with medical history of cardiac syncope or primary syncope
6. Has condition that may prolong QTc interval (for man QTc interval>450msec, for woman QTc interval>470msec) at screening
7. Pregnant or lactating woman before randomization
8. Inflammatory bowel disease (ulcerative colitis, Crohn's disease)
9. Cholestasis
10. Congestive heart failure
11. Subjects with a myocardial infarction, Unstable angina, or cerebral infarction within the latest 6 months
12. Subjects has a diagnosis of NYHA grade III-IV status
13. AST or ALT is 3.0 times higher than the upper limit of the normal range
14. Active hepatitis Or Liver cirrhosis
15. Subjects with Hyperkalemia (K>5.5 mEq/L)
16. Subjects with Renal Artery stenosis
17. Subjects with Malignancy within the 5 years at the time of screening visit(except for treated Basal cells carcinoma or squamous cell carcinoma)
18. Urinary tract disease (urinary tract infection, Neurogenic bladder)
19. Kidney disease (nephritis, chronic glomerulonephritis or polycystic kidney disease)
20. Has an allergic history to probucol
21. HbA1c > 9%
22. Systolic blood pressure ≥ 160 mmHg or Diastolic blood pressure ≥ 100 mmHg
23. Subjects taken probucol within 3 months prior to Screening
24. The subject has received an investigational product or biological agent within 3 months prior to screening
25. Subjects otherwise judged by the investigator or sub investigator to be inappropriate for inclusion in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probucol 250mg/day; Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks	Drug: Probucol 250mg/day; Probucol 250mg + Placebo; Other Names: Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks
Experimental: Probucol 500mg/day; Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks	Drug: Probucol 500mg/day; Probucol 500mg + Placebo; Other Names: Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks
Placebo Comparator: Placebo; Placebo group: placebo 2 tablets, 16 weeks	Drug: Placebo; Probucol matching placebo; Other Names: placebo 2 tablets, 16 weeks

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Cholesterol	The change in the Total cholesterol from baseline to the end of treatment(16 week)	16 week
Triglyceride	The change in the Triglyceride from baseline to the end of treatment(16 week)	16 week
LDL-C	The change in the LDL-C from baseline to the end of treatment(16 week)	16 week
HDL-C	The change in the HDL-C from baseline to the end of treatment(16 week)	16 week
oxidized LDL	The change in the oxidized LDL from baseline to the end of treatment(16 week)	16 week
d-ROM	The change in the d-ROM from baseline to the end of treatment(16 week)	16 week
urinary fibronectin	The change in the urinary fibronectin from baseline to the end of treatment(16 week)	16 week
urinary transferrin	The change in the urinary transferrin from baseline to the end of treatment(16 week)	16 week
insulin	The change in the insulin from baseline to the end of treatment(16 week)	16 week
c-peptide	The change in the c-peptide from baseline to the end of treatment(16 week)	16 week

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Chair: MoonKyu Lee, professor, Samsung Medical Center

Publications and helpful links

General Publications

• Jin SM, Han KA, Yu JM, Sohn TS, Choi SH, Chung CH, Park IeB, Rhee EJ, Baik SH, Park TS, Lee IK, Ko SH, Hwang YC, Cha BS, Lee HW, Nam MS, Lee MK. Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Arterioscler Thromb Vasc Biol. 2016 Oct;36(10):2108-14. doi: 10.1161/ATVBAHA.116.308034. Epub 2016 Aug 4.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: October 31, 2012
• First Submitted That Met QC Criteria: November 11, 2012
• First Posted (Estimate): November 15, 2012

Study Record Updates

• Last Update Posted (Actual): May 3, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Diabetic nephropathy; Probucol; Albumin creatinine ratio
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antioxidants; Probucol
• Other Study ID Numbers: 009-KOA-1201i