Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00995930
• Other study ID #: CACZ885I2206
• Secondary ID: 2009-014618-80
• Status: Completed
• Phase: Phase 2
• First received: October 15, 2009
• Last updated: June 1, 2015
• Start date: December 2009
• Est. completion date: February 2014

Study information

• Verified date: June 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGermany: Paul-Ehrlich-InstitutUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the effect of ACZ885 on vascular function in patients with documented atherosclerotic disease and T2DM or IGT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Prediabetic State

Intervention

Drug:
• ACZ885
ACZ885 150 mg was administered subcutaneously once a month for 12 months.
• Placebo
Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Montreal	Quebec
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Neuss
Germany	Novartis Investigative Site	Ulm
Israel	Novartis Investigative Site	Jerusalem
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Oxford	UK
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events, Serious Adverse Events and Death	Participants were monitored for adverse events, serious adverse events and death throughout the study.	12 months	Yes
Primary	Change From Baseline in Aortic Distensibility	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.	baseline, 3 months, 12 months	No
Primary	Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area)	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.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error	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.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in Plaque Composition	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.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in Aortic Strain	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..	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)	Blood samples were collected to analyze hsCRP.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in Fasting Plasma Glucose	Blood samples were collected to analyze fasting plasma glucose.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in Hemoglobin A1c (HbA1c)	Blood samples were collected to analyze HbA1c.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT)	Blood samples were collected to analyze the 2 hour glucose post OGTT.	baseline, 3 months, 12 months	No
Secondary	Change From Baseline in Beta Cell Function (HOMA-B)	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)].	baseline, 3 months, 12 months	No
Secondary	Change From Baseline Insulin Resistance (HOMA-IR)	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].	baseline, 3 months, 12 months	No
Secondary	Pharmacokinetics: ACZ885 Serum Concentrations	Blood samples were collected to analyze the ACZ885 serum concentrations.	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	No