Time Course of the Antiproteinuric and Blood Pressure Lowering Effects After Initiation of Renin Inhibition With Aliskiren in Type 2 Diabetes

Diabetes Type 2 Clinical Trial

Official title:

An Open-label, One-period, One-treatment Study to Evaluate the Time Course of the Antiproteinuric and Blood Pressure Lowering Effects After Initiation of Renin Inhibition With Aliskiren in Type 2 Diabetes Suffering From Incipient and/or Established Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461136
• Other study ID #: CSPP100A2242
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 16, 2007
• Last updated: September 22, 2016
• Start date: August 2005
• Est. completion date: November 2006

Study information

• Verified date: September 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2006
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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/exclusion criteria may apply

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Type 2

Intervention

Drug:
• Aliskiren

Locations

Country	Name	City	State
Denmark	Novartis	Gentofte

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To measure blood pressure changes over time during the onset and offset of effect.
Secondary	To investigate whether there is a change on biomarkers of inflammation and cardiovascular risk.