Diabetes Mellitus, Type 2
Conditions
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
Brief summary
This study will assess the optimal renoprotective dose of Aliskiren in hypertensive type 2 diabetes patients with incipient or overt nephropathy
Interventions
DRUGAliskiren
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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. * 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Investigate the antiproteinuric effect of increasing doses of Aliskiren compared to matching placebo. | End of study |
Secondary
| Measure | Time frame |
|---|---|
| Assess the effect on Glomerular Filtration Rate (GFR) of multiple dose administration of Aliskiren. | End of study |
| Assess the effect on blood pressure of multiple dose administration of Aliskiren. | End of study |
| To investigate whether there is a change in biomarkers of inflammation and cardiovascular risk. | End of study |
Countries
Denmark
Outcome results
None listed