The Effects of Bindarit in Diabetic Nephropathy

This study has been completed.
Sponsor:
Collaborator:
Mario Negri Institute for Pharmacological Research
Information provided by:
Aziende Chimiche Riunite Angelini Francesco S.p.A
ClinicalTrials.gov Identifier:
NCT01109212
First received: April 8, 2010
Last updated: April 22, 2010
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Diabetic Nephropathy
Drug: Bindarit
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of the Association Bindarit + Irbesartan Versus Irbesartan Alone on Albuminuria on Patients With Diabetic Nephropathy. Placebo-controlled Study

Resource links provided by NLM:


Further study details as provided by Aziende Chimiche Riunite Angelini Francesco S.p.A:

Primary Outcome Measures:
  • Urinary Albumin Excretion (µg/min) levels in the overnight urine specimen. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Relative change (per cent change) in Urinary Albumin Excretion (UAE) from the baseline


Secondary Outcome Measures:
  • Urinary Monocyte Chemoattractant protein (MCP-1/CCL2)(pg/ml) levels in the overnight urine specimen. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Relative change (per cent change) in Urinary MCP-1 levels from the baseline.

  • Serum lipids [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Relative change (per cent change) in total cholesterol, cholesterol HDL, triglycerides, apolipoprotein-A, apolipoprotein-B from the baseline.

  • Safety and tolerability of bindarit in association of irbesartan. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Changes in anthropometrics, laboratory parameters and vital signs from the baseline. Number of adverse events.

  • Albuminuria remission rates [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Rate of remission from macro to microalbuminuria and from micro to normoalbuminuria.


Enrollment: 100
Study Start Date: March 2007
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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
Other Name: 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.
  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01109212

Locations
Italy
The Mario Negri Institute for Pharmacological Research- Clinical Research Center for Rare Diseases
Ranica, Bergamo, Italy, 24020
Azienda Ospedaliera di Treviglio-Caravaggio - Unità Operativa Malattie Metaboliche e Diabetologia
Treviglio, Bergamo, Italy, 24047
Azienda Ospedaliera OO.RR. Bergamo - Unità Operativa Diabetologia
Bergamo, Italy, 24128
IRCCS Fondazione Centro S. Raffaele del Monte Tabor- Unità Operativa Medicina Generale
Milano, Italy, 20132
Ist. Patologia Medica e metodologia Clinica - Università di Sassari
Sassari, Italy, 7100
Slovenia
University Medical Center Dpt Endocrinology Diabetes and Metabolic Diseases- Diabetology Unit
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
Aziende Chimiche Riunite Angelini Francesco S.p.A
Mario Negri Institute for Pharmacological Research
Investigators
Principal Investigator: Giuseppe Remuzzi, PhD Mario Negri Institute for Pharmacological Research
  More Information

Additional Information:
No publications provided

Responsible Party: Aziende Chimiche Riunite Angelini Francesco S.p.A, Research Center S.Palomba-Pomezia New Products Clinical Development Department
ClinicalTrials.gov Identifier: NCT01109212     History of Changes
Other Study ID Numbers: 004SC06084, 2006-006191-38
Study First Received: April 8, 2010
Last Updated: April 22, 2010
Health Authority: Italy: The Italian Medicines Agency
Slovenia: Agency for Medicinal Products - Ministry of Health

Keywords provided by Aziende Chimiche Riunite Angelini Francesco S.p.A:
Type 2-Diabetic Nephrophaty
bindarit
albuminuria
MCP-1

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Irbesartan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014