The Effects of Bindarit in Diabetic Nephropathy

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Drug: Bindarit; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24128
    • Azienda Ospedaliera OO.RR. Bergamo - Unità Operativa Diabetologia
  • Milano, Italy, 20132
    • IRCCS Fondazione Centro S. Raffaele del Monte Tabor- Unità Operativa Medicina Generale
  • Sassari, Italy, 7100
    • Ist. Patologia Medica e metodologia Clinica - Università di Sassari
  • Bergamo
    • Ranica, Bergamo, Italy, 24020
      • The Mario Negri Institute for Pharmacological Research- Clinical Research Center for Rare Diseases
    • Treviglio, Bergamo, Italy, 24047
      • Azienda Ospedaliera di Treviglio-Caravaggio - Unità Operativa Malattie Metaboliche e Diabetologia
• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Center Dpt Endocrinology Diabetes and Metabolic Diseases- Diabetology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Collaborators: Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Giuseppe Remuzzi, PhD, Mario Negri Institute for Pharmacological Research

Publications and helpful links

Helpful Links

• Sponsor's website

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: April 8, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 23, 2010

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: albuminuria; MCP-1; Type 2-Diabetic Nephrophaty; bindarit
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Protein Synthesis Inhibitors; Bindarit
• Other Study ID Numbers: 004SC06084; 2006-006191-38 (EudraCT Number)