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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

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

Intervention(s) in this Clinical Trial

• Drug: Aliskiren

Primary 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 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

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Novartis

Overall Clinical Trial Officials and Contacts

Novartis Principal Investigator Investigative site  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00464880

Study ID Number: CSPP100A2243

ClinicalTrials.gov Identifier: NCT00464880

Health Authority: Denmark: Danish Medicines Agency