Status:

COMPLETED

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

Lead Sponsor:

Novartis

Conditions:

Diabetes Mellitus, Type 2

Eligibility:

All Genders

30-80 years

Phase:

PHASE1

PHASE2

Brief 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

  • 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:
  • 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)
  • 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

  • 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

Key Trial Info

Start Date :

October 1 2005

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

Estimated Enrollment :

26 Patients enrolled

Trial Details

Trial ID

NCT00464776

Start Date

October 1 2005

Last Update

February 4 2011

Active Locations (1)

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1

Novartis

Gentofte Municipality, Denmark, 2820