The Effects of Bindarit in Diabetic Nephropathy
The Effects of Bindarit in Diabetic Nephropathy
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.