Hypertension
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and/or female patients from 30-80 years of age with a diagnosis of Type 2 diabetes (WHO criteria). 2. Incipient and established diabetic nephropathy (urinary albumin excretion = 100 mg/day but = 2000 mg/day). Investigator should make an effort to have two subgroups (incipient and established nephropathy) as balance as possible, but at least 5 patients in each subgroup. 3. GFR = 40 ml/min (estimated using MDRD formula) in the last 4 months. 4. Female patients must be postmenopausal (i.e. must have had no regular menstrual bleeding for at least 1 years prior to inclusion) or must have had a bilateral oophorectomy or must have been surgically sterilized or hysterectomized at least 6 months prior to screening. Menopause will be confirmed by a plasma 17ß-estradiol concentration of 40 IU/L. Surgical sterilization procedures or hysterectomy must be supported with clinical documentation made available to the sponsor. 5. To be eligible patients must fulfill the following criteria a) Patients on ongoing hypertensive therapy must have a blood pressure = 135/85 mm Hg but lower than 170/105 mm Hg at baseline (Day -1) AND patients must be on stable antihypertensive medications for at least 8 weeks prior to baseline (Day -1). b) Newly diagnosed hypertensive patients must have a blood pressure = 135/85 mm Hg but lower than 170/105 mm Hg at baseline (Day -1). 6. Patients must be on stable hypoglycemic medications for at least 8 weeks prior to Visit 2 ( Day -1). 7. Patients must be willing and medically able to discontinue all ACEI, ARB, aldosterone receptor antagonist and potassium sparing diuretic medications for the duration of the study. 8. Oral body temperature within the range 35.0-37.5 °C 9. Able to provide written informed consent prior to study participation. Patient information and consent forms generated by the investigator must be approved by the sponsor prior to submission to the Ethics Committee (EC)/Institutional Review Board (IRB). A copy of the patient information and consent forms approved by the EC/IRB must be forwarded to the sponsor prior to study initiation. 10. Able to communicate well with the investigator and comply with the requirements of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria during screening or baseline evaluations will be excluded from entry into or continuation in the study: 1. Severe Hypertension Grade 3 WHO classification (MSDBP ? 110 mmHg and/or MSSBP ? 180 mmHg) 2. ASA treatment >1g/day or regular use of NSAIDs 3. Kidney disease not caused by diabetes or hypertension 4. Serum potassium 5.1 mEq/L 5. GFR 11 %) 15. History of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years 16. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. 17. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing. 18. Significant illness within the two weeks prior to dosing. 19. Significant illness within the two weeks prior to dosing. 20. 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 as determined by any one of the following: SGOT/AST or SGPT/ALT values exceeding 2 x ULN at Visit 1, and Gamma GT x 3 ULN at Visit 1 a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt • Current treatment with cholestyramine or cholestipol resins 21. History of immunocompromise, including a positive HIV (ELISA and Western blot) test result. 22. History of a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 23. History of drug or alcohol abuse within the 12 months prior to dosing. 24. Persons directly involved in the execution of this protocol. 25. Any condition that in the opinion of the investigator or the Novartis medical monitor would jeopardize the evaluation of efficacy or safety 26. History of noncompliance to medical regimens or unwillingness to comply with the study protocol 27. 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 28. 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 t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To investigate the time course of the antiproteinuric and blood pressure lowering effect of renin inhibition with Aliskiren in patients with Type 2 diabetes suffering from incipient and/or established nephropathy;Secondary Objective: • To measure blood pressure changes over time during the onset and offset of effect. • To investigate whether there is a change on biomarkers of inflammation and cardiovascular risk. ;Primary end point(s): Pharmacodynamic assessment of the time-course of the antiproteinuric effect of renin inhibition with Aliskiren in patients with Type 2 diabetes suffering from incipient and/or established nephropathy | — |
Countries
Denmark
Outcome results
None listed