Clinical trial NCT01726816: Efficacy and Safety Study of Probucol in Patients With Diabetic Nephropathy
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathy
Keywords: Diabetic nephropathy
Albumin creatinine ratio
Probucol
Lead sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2012-11-15
Enrollment: 126
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: A/C ratio
timeFrame: 16 week
Secondary outcomes:
measure: Serum creatinine
timeFrame: 16 week
measure: eGFR
timeFrame: 16 week
measure: cystatin C
timeFrame: 16 week
measure: urine albumin
timeFrame: 16 week
measure: P/C ratio
timeFrame: 16 week
Other outcomes:
measure: Total Cholesterol
timeFrame: 16 week
measure: Triglyceride
timeFrame: 16 week
measure: LDL-C
timeFrame: 16 week
measure: HDL-C
timeFrame: 16 week
measure: oxidized LDL
timeFrame: 16 week
measure: d-ROM
timeFrame: 16 week
measure: urinary fibronectin
timeFrame: 16 week
measure: urinary transferrin
timeFrame: 16 week
measure: insulin
timeFrame: 16 week
measure: c-peptide
timeFrame: 16 week
Locations:
city: Bucheon
country: Korea, Republic of
facility: The Catholic university of Korea, Bucheon St. Mary's Hospital
city: DaeGu
country: Korea, Republic of
facility: Kyungpook National University
city: DaeGu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Incheon
country: Korea, Republic of
facility: Gil Hospital
city: InCheon
country: Korea, Republic of
facility: Inha University Hospital
city: JeonJu
country: Korea, Republic of
facility: Chonbuk national University Hospital
city: Seoul
country: Korea, Republic of
facility: Eulji Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Kangnam Sacred Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Kyunghee Univ Hospital at Kangdong
city: Seoul
country: Korea, Republic of
facility: Samsumg Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: SungNam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Suwon
country: Korea, Republic of
facility: St. Vincent Hospital
city: Uijeongbu
country: Korea, Republic of
facility: UIJEONGBU ST. MARY's HOSPITAL
Study officials:
affiliation: Samsung Medical Center
name: MoonKyu Lee, professor
role: STUDY_CHAIR
References:
citation: 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.