- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00995930
Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients
June 1, 2015 updated by: Novartis Pharmaceuticals
A Multi-center, Randomized , Double Blind, Placebo-controlled, Study of the Safety, Tolerability, and Effects on Arterial Structure and Function of ACZ885 in Patients With Clinically Evident Atherosclerosis and Either T2DM or IGT
This study will evaluate the effect of ACZ885 on vascular function in patients with documented atherosclerotic disease and T2DM or IGT.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
189
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Quebec
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Montreal, Quebec, Canada, H1T 1C8
- Novartis Investigative Site
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Mainz, Germany, 55116
- Novartis Investigative Site
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Neuss, Germany, 41460
- Novartis Investigative Site
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Ulm, Germany, 89081
- Novartis Investigative Site
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Jerusalem, Israel, 91120
- Novartis Investigative Site
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London, United Kingdom, EC1M 6BQ
- Novartis Investigative Site
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UK
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Oxford, UK, United Kingdom, OX2 6HE
- Novartis Investigative Site
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New York
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New York, New York, United States, 10029
- Novartis Investigative Site
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Ohio
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Cincinnati, Ohio, United States, 45219
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 74 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients with known atherosclerotic disease and documented diagnosis of T2DM for ≤ 14 years OR IGT
- HbA1c between 6.0% and 10.0%
- On stable statin therapy or statin intolerant
- Patients who are eligible and able to participate in the study
Exclusion Criteria:
- Contraindications to MRI
- NYHA class IV Heart Failure
- NYHA class I - III heart failure with acute exacerbation in 3 months prior to screening
- Patients with type 1 diabetes
- Acute infections
- HsCRP > 30 mg/dL
- Aortic aneurysm ≥5cm
Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
subcutaneous (SQ) monthly
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Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.
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Experimental: ACZ885
150 mg SQ monthly
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ACZ885 150 mg was administered subcutaneously once a month for 12 months.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Time Frame: 12 months
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Participants were monitored for adverse events, serious adverse events and death throughout the study.
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12 months
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Change From Baseline in Aortic Distensibility
Time Frame: baseline, 3 months, 12 months
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Two axial, ECG-gated, steady state free precession (SSFP) 'cine' images were acquired during breath-hold to determine aortic distensibility.
The first image was obtained at the level of the right pulmonary artery through the ascending and proximal descending aorta and the second through the distal aorta below the diaphragm.
Imaging of the aorta also enabled evaluation of the plaque burden and additional vascular function measures.
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baseline, 3 months, 12 months
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Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area)
Time Frame: baseline, 3 months, 12 months
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For assessment of atherosclerotic plaque burden of the aorta, vessel wall images of the aorta were acquired with an ECG gated double-inversion recovery (black blood) fast spin echo sequence applied breath-holding.
Using an oblique sagittal image of the aorta as a pilot, serial axial images were acquired to cover a section of the descending thoracic aorta.
The midpoint of the right pulmonary artery in cross section was used as the anatomical reference for the first slice in baseline and follow-up scans.
For assessment of the atherosclerotic plaque burden in the carotids, vessel wall images were acquired with an axial ECG gated PD (proton density) weighted black blood sequence.
The carotid bifurcation was used as the anatomical reference for all three imaging time points (baseline, 12 weeks, 48 weeks) with axial slice planes acquired below the bifurcation region.
The mean values reported here for the carotid are reported for the proximal common carotid region.
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baseline, 3 months, 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error
Time Frame: baseline, 3 months, 12 months
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Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location.
The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity.
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baseline, 3 months, 12 months
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Change From Baseline in Plaque Composition
Time Frame: baseline, 3 months, 12 months
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During the carotid MRI acquisition, in addition to the PD weighted ECG gated double inversion fast spin echo sequences T1 and T2 weighted sequences were acquired.
In combination with the PD weighted images, the multi-contrast images were analyzed to determine regions of interest with contrast patterns consistent with the presence of necrotic lipid core, calcification and fibrous tissue in participants who had complex carotid plaque present in the bifurcation region.
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baseline, 3 months, 12 months
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Change From Baseline in Aortic Strain
Time Frame: baseline, 3 months, 12 months
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Arterial strain was computed directly from the cine SSFP images and the change in lumen diameters over the cardiac cycle.
The value was independent of pulse pressure and is unitless ratio derived from the maximum to minimum lumen diameters diastole and systole, respectively..
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baseline, 3 months, 12 months
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Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
Time Frame: baseline, 3 months, 12 months
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Blood samples were collected to analyze hsCRP.
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baseline, 3 months, 12 months
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Change From Baseline in Fasting Plasma Glucose
Time Frame: baseline, 3 months, 12 months
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Blood samples were collected to analyze fasting plasma glucose.
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baseline, 3 months, 12 months
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Change From Baseline in Hemoglobin A1c (HbA1c)
Time Frame: baseline, 3 months, 12 months
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Blood samples were collected to analyze HbA1c.
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baseline, 3 months, 12 months
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Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT)
Time Frame: baseline, 3 months, 12 months
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Blood samples were collected to analyze the 2 hour glucose post OGTT.
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baseline, 3 months, 12 months
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Change From Baseline in Beta Cell Function (HOMA-B)
Time Frame: baseline, 3 months, 12 months
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Blood samples were collected to analyze beta cell function.
Beta cell function was calculated by the Homeostasis Model Assessments (of beta cell function (HOMA-B) as follows: HOMA-B: The product of 20 and basal insulin (µU/mL) levels divided by the value of basal glucose (mmol/L) concentrations minus 3.5 [i.e., HOMA-B = 20*basal insulin/(basal glucose-3.5)].
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baseline, 3 months, 12 months
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Change From Baseline Insulin Resistance (HOMA-IR)
Time Frame: baseline, 3 months, 12 months
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Blood samples were collected to analyze insulin resistance.
Insulin resistance was calculated by the Homeostasis Model Assessments of insulin resistance (HOMA-IR)) as follows: HOMA-IR: The product of basal glucose (mmol/L) and insulin (µU/mL) levels divided by 22.5 [i.e., HOMA-IR = basal glucose*basal insulin/22.5].
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baseline, 3 months, 12 months
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Pharmacokinetics: ACZ885 Serum Concentrations
Time Frame: pre-dose, 0.167 day post dose 1, 7 days post dose 1, 14 days post dose 1, every 30 days post each dose from doses 1 through 12, 60 days post dose 12, 90 days post dose 12
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Blood samples were collected to analyze the ACZ885 serum concentrations.
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pre-dose, 0.167 day post dose 1, 7 days post dose 1, 14 days post dose 1, every 30 days post each dose from doses 1 through 12, 60 days post dose 12, 90 days post dose 12
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2009
Primary Completion (Actual)
February 1, 2014
Study Completion (Actual)
February 1, 2014
Study Registration Dates
First Submitted
October 15, 2009
First Submitted That Met QC Criteria
October 15, 2009
First Posted (Estimate)
October 16, 2009
Study Record Updates
Last Update Posted (Estimate)
June 29, 2015
Last Update Submitted That Met QC Criteria
June 1, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CACZ885I2206
- 2009-014618-80
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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