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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00464776
First received: April 21, 2007
Last updated: February 3, 2011
Last verified: February 2011
  Purpose

This study will assess the optimal renoprotective dose of Aliskiren in hypertensive type 2 diabetes patients with incipient or overt nephropathy


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Aliskiren
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Cross-over, 4-period, 4 Treatment, Within-subject Placebo-controlled Study to Assess the Optimal Renoprotective Dose of Aliskiren in Hypertensive Type 2 Diabetic Patients With Incipient or Overt Nephropathy

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Investigate the antiproteinuric effect of increasing doses of Aliskiren compared to matching placebo. [ Time Frame: End of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the effect on Glomerular Filtration Rate (GFR) of multiple dose administration of Aliskiren. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Assess the effect on blood pressure of multiple dose administration of Aliskiren. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • To investigate whether there is a change in biomarkers of inflammation and cardiovascular risk. [ Time Frame: End of study ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: October 2005
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Various sequences of 3 doses of Aliskiren plus placebo
Drug: Aliskiren
Other Name: SPP100
Experimental: 2
Various sequences of 3 doses of Aliskiren plus placebo
Drug: Aliskiren
Other Name: SPP100
Experimental: 3
Various sequences of 3 doses of Aliskiren plus placebo
Drug: Aliskiren
Other Name: SPP100
Experimental: 4
Various sequences of 3 doses of Aliskiren plus placebo
Drug: Aliskiren
Other Name: SPP100

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 < 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00464776

Locations
Denmark
Novartis
Gentofte, Denmark, 2820
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Investigative site
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00464776     History of Changes
Other Study ID Numbers: CSPP100A2240
Study First Received: April 21, 2007
Last Updated: February 3, 2011
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Novartis:
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

Additional relevant MeSH terms:
Diabetes Mellitus
Kidney Diseases
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014