The purpose of this study is to determine whether bindarit is effective to reduce albuminuria, compared to placebo, in nephropathic patients treated with irbesartan, as a background therapy.

This is a pilot phase II, double-blind, multicentre, randomized, placebo-controlled, parallel groups study in patients with DN undergoing irbesartan therapy.

According to screening urinary albumin excretion, at baseline and before randomization, all patients will be categorized into 2 strata:

Stratum 1: microalbuminuria (20 to 200 μg/min, in at least 2 of 3 consecutive overnight urine samples collected at the screening) Stratum 2: macroalbuminuria (>200 μg/min, in at least 2 of 3 consecutive overnight urine samples collected at the screening).

Within each stratum, patients will be randomly allocated on a 1:1 basis to the 2 treatment arms (after one month induction period):

• bindarit 600MG twice a day
• placebo All patients will be treated with irbesartan 300 mg/day as background therapy. After 12 months of treatment albuminuria will be evaluated as primary endopoint.

INCLUSION CRITERIA

• male and female patients with no limitation of race, aged 30 to 70 years;
• Type 2 diabetes defined as: > 30 years of age at diagnosis; insulin not required within 6 months of initial diagnosis; no history of diabetic ketoacidosis; currently treated with diet, oral hypoglycemics or insulin [Brenner 2000];
• microalbuminuria defined as urinary albumin excretion, 20 to 200 µg/min in at least 2 of 3 overnight urine samples or macroalbuminuria defined as urinary albumin excretion, > 200 µg/min in at least 2 of 3 overnight urine samples, confirmed in the baseline collection; should baseline albuminuria data not to be available, the patient may be conditionally treated;
• glycosylated haemoglobin (Hb A1c) <12% at Screening [Brenner 2000];
• serum creatinine ≤ 3 mg/dL at Screening;
• normotensive patients or hypertensive patients on stable antihypertensive therapy over the last 3 months and without specific contraindications to angiotensin antagonist therapy;
• female patients of childbearing potential required to have a negative pregnancy test and use an approved birth control method;
• patients legally able to give written informed consent to the trial (signed and dated by the patient).

EXCLUSION CRITERIA

Patients cannot enter the trial under the following circumstances:

• patients hypersensitive or allergic to ARBs or bindarit or its components, or with a positive history for drug allergy;
• Type 1 diabetes [Brenner 2000];
• history of non diabetic renal disease, including renal artery stenosis [Brenner 2000];
• history of heart failure before enrolment [Brenner 2000];
• acute myocardial infarction, coronary artery bypass grafting within the past one month [Brenner 2000];
• cerebral vascular accident or coronary angioplasty within the past six months month [Brenner 2000];
• Transient Ischemic Attacks (TIA) in the past 12 months [Brenner 2000];
• primary aldosteronism or pheocromocytoma [Brenner 2000];
• severe uncontrolled hypertension (sitting diastolic blood pressure > 115 and/or sitting systolic blood pressure> 220 mm Hg) in the previous 6 months;
• chronic use of corticosteroids, non-steroidal anti-inflammatory drugs, immunosuppressive drugs, MAO inhibitors;
• patients under the influence of alcohol or narcotics;
• patients treated with experimental drugs in the previous 4 weeks.