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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Kidney Diseases
Diabetic Nephropathies
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 September 18, 2014