Effects of Aliskiren, Irbesartan, and the Combination in Hypertensive Patients With Type 2 Diabetes and Diabetic Nephropathy

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00464880
First received: April 21, 2007
Last updated: November 28, 2007
Last verified: November 2007
  Purpose

This study will assess the reno-protective effect of renin inhibition with aliskiren as an alternative to irbesartan in type 2 diabetes patients with incipient/overt diabetic nephropathy.


Condition Intervention Phase
Diabetes Type 2
Drug: Aliskiren
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Parallel-Group, Cross-Over, 4-Period, 4 Treatment, Within-Subject Placebo-Controlled Study to Assess the Reno-Protective Effect of Renin Inhibition With Aliskiren as an Alternative to Irbesartan in Type 2 Patients With Incipient/Overt Diabetic Nephropathy

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To investigate whether renin-inhibition using aliskiren 300 mg daily could be a treatment alternative to the angiotensin II receptor antagonist irbesartan 300 mg with an equivalent potential for reno-protection

Secondary Outcome Measures:
  • To investigate whether combination therapy using aliskiren 300 mg daily and irbesartan 300 mg daily has a greater effect on reno-protection than either drug alone
  • To investigate whether aliskiren, irbesartan or the combination reduce biomarkers of inflammation and cardiovascular risk

Estimated Enrollment: 24
Study Start Date: September 2005
Study Completion Date: November 2007
Detailed Description:

Antiproteinuric Effects of Aliskiren (Renin Inhibitor), Irbesartan (Angiotensin Receptor Antagonist) and the Combination in Hypertensive Patients With Type 2 Diabetes and Incipient/Overt Diabetic Nephropathy

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and/or female subjects between the ages of 30-80 years with a diagnosis of type 2 diabetes (World Health Organization criteria)
  • Body mass index (BMI) within the range of 20 and 32.
  • Incipient or overt diabetic nephropathy (urinary albumin excretion ≥ 100 but ≤ 2000 mg/day).
  • Glomerular filtration rate (GFR) ≥ 40 ml/min documented in the last 4 months prior to randomization
  • To be eligible for randomization, patients must fulfill the following criteria:

    1. Patients on ongoing hypertensive therapy must have a blood pressure ≥ 135/85 mmHg but lower than 170/105 mmHg at Visit 2 (Day -1) AND patients must be on stable antihypertensive medications for at least 8 weeks prior to Visit 2 (run-in period).
    2. Newly diagnosed hypertensive patients must have a blood pressure ≥ 135/85 mmHg but lower than 170/105 mmHg at Visit 2 (Day -1).
  • Patients must be on stable hypoglycemic medications for at least 8 weeks prior to Visit 2 (Day -1).
  • Patients must be willing and medically able to discontinue all angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), aldosterone receptor antagonist and potassium sparing diuretic medications for the duration of the study.
  • Female patients must be postmenopausal, have had a bilateral oophorectomy, or have been surgically sterilized or hysterectomized at least 6 months prior to screening.
  • Oral body temperature within the range of 35.0-37.5 °C
  • Able to provide written informed consent prior to study participation.
  • Able to communicate well with the investigator and comply with the requirements of the study.

Exclusion Criteria:

  • Severe hypertension, Grade 3 World Health Organization (WHO) classification (mean sitting diastolic blood pressure [MSDBP] ≥ 110 mmHg and/or mean sitting systolic blood pressure [MSSBP] ≤ 180 mmHg)
  • Acetylsalicylic acid (ASA) treatment > 1 g/day or regular use of nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Kidney disease not caused by diabetes or hypertension
  • Serum potassium < 3.5 or > 5.1 mEq/L
  • GFR < 40 ml/min/1.73m2 as measured by the Modification of Diet in Renal Disease (MDRD) formula
  • Serum albumin < 2.0 mg/dL
  • History of hypertensive encephalopathy or cerebrovascular accident in the last 12 months prior to Visit 1
  • Transient ischemic cerebral attack during the 6 months prior to Visit 1
  • Current diagnosis of heart failure (New York Heart Association [NYHA] Class II-IV)
  • History of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to Visit 1
  • Second or third degree heart block without a pacemaker
  • Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia
  • Clinically significant valvular heart disease
  • Type 1 diabetes mellitus
  • Uncontrolled type II diabetes mellitus; hemoglobin subtype A1C (HbA1C) > 11%
  • History of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years
  • Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
  • Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
  • Significant illness within the two weeks prior to dosing.
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following:

    • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
    • Currently active or previously active inflammatory bowel disease during the 12 months prior to Visit 1
    • Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1.
    • Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
    • Evidence of hepatic disease, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portacaval shunt
    • Current treatment with cholestyramine or colestipol resins
  • History of immunocompromise, including a positive test result.
  • History of a positive hepatitis B surface antigen (HBsAg) or hepatitis C test result.
  • History of drug or alcohol abuse within the 12 months prior to dosing.
  • Persons directly involved in the execution of this protocol.
  • Any condition that, in the opinion of the investigator or the Novartis medical monitor, would jeopardize the evaluation of efficacy or safety
  • History of noncompliance to medical regimens or unwillingness to comply with the study protocol
  • Known or suspected contraindications to the study medications, including history of allergy to ACE inhibitors and/or to thiazide diuretics or other sulfonamide derived drug
  • Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
  • Use of any prescription drug or over-the-counter (OTC) medication which is prohibited by the protocol.
  • Patients who previously participated in any aliskiren study.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00464880

Locations
Denmark
Novartis
Gentofte, Denmark, 2820
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Investigative site
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00464880     History of Changes
Other Study ID Numbers: CSPP100A2243
Study First Received: April 21, 2007
Last Updated: November 28, 2007
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Novartis:
Placebo-controlled study
assess the renoprotective effect of renin inhibition
Aliskiren as an alternative to irbesartan
Type 2 diabetes patients
incipient/overt diabetic nephropathy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Kidney Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
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