Diabetes Type 2
Conditions
Keywords
Time course, antiproteinuric, blood pressure, lowering effect, initiation of renin inhibition, Aliskiren in Type 2 diabetes, incipient and/or established nephropathy
Brief summary
This study will evaluate 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.
Interventions
DRUGAliskiren
Sponsors
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and/or female patients from 30-80 years of age with a diagnosis of Type 2 diabetes (WHO criteria). * Incipient and established diabetic nephropathy (urinary albumin excretion ≥ 100 mg/day but ≤ 2000 mg/day). * Glomerular filtration rate (GFR) ≥ 40 ml/min (estimated using Modification of Diet in Renal Disease (MDRD) formula) in the last 4 months. * 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. * To be eligible patients must fulfill the following criteria: 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).; Newly diagnosed hypertensive patients must have a blood pressure ≥ 135/85 mm Hg but lower than 170/105 mm Hg at baseline (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. * 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.
Exclusion criteria
* 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 drug (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 MDRD formula * Serum albumin \< 2.0mg/dL * History of hypertensive encephalopathy or cerebrovascular accident at any time prior to Visit1. * 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 (Hemaglobin 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 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 Angiotensin converting enzyme (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. * Pregnant or nursing woman. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Denmark
Outcome results
None listed