study to assess the optimal renoprotective dose of aliskiren in hypertensive patients with type 2 diabetes and incipient or overt nephropathy

Conditions: Diabetes Mellitus, Type 2

Summary: this study will assess the optimal renoprotective dose of aliskiren in hypertensive type 2 diabetes patients with incipient or overt nephropathy


Eligibility criteria:
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 \ 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

Keywords: randomized double-blind cross-over 4-period 4 treatment within-subject placebo-controlled study assess optimal renoprotective dose of aliskiren hypertensive type 2 diabetes patients incipient or overt nephropathy