Study to Assess the Optimal Renoprotective Dose of Aliskiren in Hypertensive Patients With Type 2 Diabetes and Incipient or Overt Nephropathy

A Randomized, Double-blind, Cross-over, 4-period, 4 Treatment, Within-subject Placebo-controlled Study to Assess the Optimal Renoprotective Dose of Aliskiren in Hypertensive Type 2 Diabetic Patients With Incipient or Overt Nephropathy

This study will assess the optimal renoprotective dose of Aliskiren in hypertensive type 2 diabetes patients with incipient or overt nephropathy

Inclusion Criteria:

• Male and/or female patients from 30-80 years of age.

• Type 2 diabetes (defined using World Health Organization criteria)

• Incipient or overt nephropathy (urinary albumin excretion 100 but ≤ 2000 mg/day).

• Glomerular filtration rate (GFR) 40ml per minute

• To be eligible for randomization, patients must fulfill the following criteria:

  1. Patients on ongoing hypertensive therapy must have a blood pressure ≥ 135/85 mm Hg but lower than 170/105 mm Hg at Visit 3 (Day -1, Period 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 mm Hg but lower than 170/105 mm Hg at Visit 3 (Day -1, Period 1)

• Female patients must be postmenopausal or must have had a bilateral oophorectomy or must have been surgically sterilized or hysterectomized at least 6 months prior to screening

• Oral body temperature within the range 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.

• Patients must be willing and medically able to discontinue anti-hypertensive treatment or any other medication which is prohibited in the study protocol.

• Patients must be on stable hypoglycemic medications for at least 8 weeks prior to visit 1 (Screening visit).

Exclusion Criteria:

• Use of any prescription drug or over-the-counter (OTC) medication which is prohibited by the protocol.

• Severe Hypertension Grade 3 WHO classification Mean Sitting Diastolic Blood Pressure (MSDBP) 110 mmHg and/or Mean Sitting Systolic Blood Pressure MSSBP 180 mmHg)

• Acetylsalicyclic acid (ASA) treatment >1g/day or regular use of Non steroidal 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 < 2.0mg/dL

• History of hypertensive encephalopathy or cerebrovascular accident at any time 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

• Pregnant or nursing women

• 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 portocaval shunt
  • Current treatment with cholestyramine or cholestipol resins

• History of immunocompromise, including a positive HIV 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

• Patients who previously participated in any Aliskiren study.

Other protocol-defined inclusion/exclusion criteria may apply