The Effects of Bindarit in Diabetic Nephropathy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Effects of the Association Bindarit + Irbesartan Versus Irbesartan Alone on Albuminuria on Patients With Diabetic Nephropathy. Placebo-controlled Study

Conditions
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Diabetic Nephropathy

Intervention / Treatment
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* Drug: Bindarit
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bindarit<br>Patients treated with bindarit 2x300 mg bid plus irbesartan 2x150 mg once a day for 12 weeks | Drug: Bindarit<br>* dosage form:tablet dosage:2x300 mg frequency:b.i.d duration:12 weeks<br>* Other names: AF2838;|
| Placebo Comparator: Placebo<br>patients treated with placebo 2 tablets bid plus irbesartan 2x150 mg once a day for 12 weeks | Drug: Placebo<br>* dosage form: tablet dosage: n.a. frequency: 2xplacebo b.i.d duration:12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Albumin Excretion (µg/min) levels in the overnight urine specimen. | Relative change (per cent change) in Urinary Albumin Excretion (UAE) from the baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Monocyte Chemoattractant protein (MCP-1/CCL2)(pg/ml) levels in the overnight urine specimen. | Relative change (per cent change) in Urinary MCP-1 levels from the baseline. | 12 weeks | 
| Serum lipids | Relative change (per cent change) in total cholesterol, cholesterol HDL, triglycerides, apolipoprotein-A, apolipoprotein-B from the baseline. | 12 weeks | 
| Safety and tolerability of bindarit in association of irbesartan. | Changes in anthropometrics, laboratory parameters and vital signs from the baseline. Number of adverse events. | 12 weeks | 
| Albuminuria remission rates | Rate of remission from macro to microalbuminuria and from micro to normoalbuminuria. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2-Diabetic Nephrophaty, bindarit, albuminuria, MCP-1