Efficacy and Safety Study of Probucol in Patients With Diabetic Nephropathy

Phase 2

Completed

• Conditions: Diabetic Nephropathy
• Interventions: Drug: Probucol 250mg/day; Drug: Placebo; Drug: Probucol 500mg/day

• Registration Number: NCT01726816
• Lead Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.

Brief Summary

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

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 Timeline

• Study Start: 2012-10
• Study First Submitted: 2012-10-31
• Study First Submitted QC: 2012-11-11
• Study First Posted: 2012-11-15
• Primary Completion: 2014-04
• Study Completion: 2014-09
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-01
• Last Update Posted: 2017-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 126

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Probucol 250mg/day	Probucol 250mg/day	Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks
Placebo	Placebo	Placebo group: placebo 2 tablets, 16 weeks
Probucol 500mg/day	Probucol 500mg/day	Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks

Primary Outcome Measures

Name	Time	Method
A/C ratio	16 week	The change in the A/C ratio from baseline to the end of treatment(16 week) \[Time Frame: baseline to 16 weeks\]

Secondary Outcome Measures

Name	Time	Method
eGFR	16 week	The change in the eGFR from baseline to the end of treatment(16 week)
Serum creatinine	16 week	The change in the Serum creatinine from baseline to the end of treatment.
cystatin C	16 week	The change in the cystatin C from baseline to the end of treatment(16 week)
urine albumin	16 week	The change in the urine albumin from baseline to the end of treatment(16 week)
P/C ratio	16 week	The change in the P/C ratio from baseline to the end of treatment(16 week)

Trial Locations

Locations (16)

Kyungpook National University; 🇰🇷 DaeGu, Korea, Republic of

The Catholic university of Korea, Bucheon St. Mary's Hospital; 🇰🇷 Bucheon, Korea, Republic of

Gil Hospital; 🇰🇷 Incheon, Korea, Republic of

Inha University Hospital; 🇰🇷 InCheon, Korea, Republic of

Eulji Hospital; 🇰🇷 Seoul, Korea, Republic of

Chonbuk national University Hospital; 🇰🇷 JeonJu, Korea, Republic of

Kangbuk Samsung Hospital; 🇰🇷 Seoul, Korea, Republic of

Kangnam Sacred Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsumg Medical Center; 🇰🇷 Seoul, Korea, Republic of

Kyunghee Univ Hospital at Kangdong; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 SungNam, Korea, Republic of

UIJEONGBU ST. MARY's HOSPITAL; 🇰🇷 Uijeongbu, Korea, Republic of

St. Vincent Hospital; 🇰🇷 Suwon, Korea, Republic of

Yeungnam University Medical Center; 🇰🇷 DaeGu, Korea, Republic of