IRB Number:

08-005427

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Kidney disease develops in an estimated 10% to 40% of patients with type 2 diabetes. Although angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) have been shown to slow the progression of diabetic nephropathy and delay the onset of end-stage renal disease (ESRD), they do not prevent this ultimate outcome. In the United States and Europe, diabetic nephropathy represents the most frequent cause of ESRD.

Diabetic nephropathy, and in particular ESRD, is extremely costly, both in terms of medical treatment and lost productivity. Treatments that prevent the development or progression of diabetic nephropathy will meet a significant medical need and may provide a significant cost savings to the healthcare system.
The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study have demonstrated that intensified glycemic control reduces the development and progression of diabetic microvascular complications including nephropathy, retinopathy, and neuropathy.

One possible mechanism by which hyperglycemia-induced microvascular complications may occur is through the formation of advanced glycation end-products (AGEs). Advanced glycation end-products are formed via condensation of glucose with proteins to form a Schiff base which subsequently undergoes rearrangement to form an Amadori-intermediate. The Amadori-intermediate then undergoes oxidation to irreversibly form AGEs. By a post-Amadori mechanism, Pyridorin inhibits AGE formation and has demonstrated evidence of efficacy in preclinical models of diabetic nephropathy, as well as preliminary evidence of efficacy in patients with nephropathy and diabetes in Phase 2 clinical trials. Based on these data, Pyridorin is being further evaluated for the treatment of diabetic nephropathy due to type 2 diabetes.

Who is Eligible to Participate in the Study?

1. Patients who have given voluntary written consent to participate in this study prior to conducting Screening Visit procedures;
2. Male and female patients 25 years of age or older with a diagnosis of type 2 diabetes -- If a woman is of childbearing potential (WOCBP) she must agree to use appropriate birth control (double barrier methods, hormonal contraceptives,or intrauterine device) for the duration of the study (WOCBP is defined as all women who are not surgically sterile or are not at least 1 year postmenopausal). All WOCBP must have a negative serum pregnancy test at the Screening Visit;
3. At the Screening Visit, ALL patients must have a history of overt diabetic nephropathy, as defined by the following: a SCr (serum creatinine ratio) measurement of 1.3 mg/dL to 3.3 mg/dL (women) or 1.5 mg/dL to 3.5 mg/dL (men) inclusive, and a 24-hour urine collection PCR ≥1200 mg/g;
4. Patients must be receiving an ACE-I or an ARB for at least 3 months prior to the Qualifying Visit (Screening Visit for those patients not entering into the Optional
Run-in Period), where the dose of the ACE-I or the ARB is considered appropriate for that patient and has been stable for at least 2 months;
5. Patients must be on stable blood pressure medications for 2 months prior to the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period), with a seated blood pressure at the Qualifying Visit of ≤160/90 mmHg;
6. At the Qualifying Visit (only applies to those patients who enter into the Optional Run-in Period), the following eligibility parameters must be met in order to be randomized: A SCr measurement within 25% of the SCr measurement at the Screening Visit, and a 24-hour urine collection PCR ≥600 mg/g.

Minimum Age:

25

Maximum Age:

99

What is Involved With this Study?

During this study you will have at least 9 study visits. There is a two-week screening period to determine if you meet the requirements to be in the study. During the screening period you will be asked about your medical history. Vital signs (blood pressure and heart rate), height, and weight will be measured. Blood samples will be collected for laboratory testing. A serum pregnancy test will be done for females of childbearing potential. You will be asked about any medications you have taken, including those taken in the last 30 days. You will be given instructions on how to collect a 24-hour urine sample at home and you will be given a urine collection container.

If your blood pressure medication is not stable, you will enter the run-in period. The run-in period may last up to 4 months. This may require changes to your current blood pressure medication(s). Your study doctor may adjust your dose as many times as needed to achieve the desired blood pressure. If the study doctor decides that the blood pressure medications that you are currently taking meet the definition of stable therapy as needed for this study, you will skip the optional run-in period and move to the next phase of the study.

Once it has been determined if a patient has meet the requirements to be entered into the study the following study visits will be required: Baseline, Week 4, Week 13, Week 26, Week 39, Week 51, Week 52, Week 52/Follow up Visit. During these visits depending upon the time point you will be required to have a physical exam, vital signs taken, blood and urine testing and an ECG performed.

How long will the Study run?

You will be in the study for up to 17 months.

Who can I Contact for Additional Information on this Trial?

Shirley Jennison
Phone: (507)255-0231
Fax: (507) 255-0770
jennison.shirley@mayo.edu

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 01/29/2009