Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant (AUDITOR)

Sanofi

Status and phase

Terminated

Phase 3

Conditions

Carotid Artery Plaque

Obesity

Metabolic Syndrome X

Arteriosclerosis

Treatments

Drug: Placebo (for Rimonabant)

Drug: Rimonabant

Study type

Interventional

Funder types

Industry

Identifiers

NCT00228176

EFC5828

2005-001612-49 (EudraCT Number)

Details and patient eligibility

About

Objectives:

Primary: To evaluate the effect of rimonabant 20-mg once daily in comparison with placebo, on the quantitative progression of atherosclerosis as assessed by carotid artery intima-media thickness (CIMT)
Secondary: To evaluate the safety and tolerability of the above rimonabant regimen in the study population of atherosclerosis patients.

Full description

This is a Phase III, prospective, multicentre, multinational, randomized, double-blind, placebo-controlled, 2-arm parallel group trial (rimonabant 20-mg od vs placebo). There will be a three-stage screening process including successively a Screening visit, a Screening CIMT and a validation of the Screening CIMT by the Imaging Core Laboratory. Patients complying with all inclusion and exclusion criteria will be randomized in one of the 2 treatment groups less than two weeks after Screening visit. Study drug (rimonabant 20 mg od or matching placebo) will be administered during 30 to 32 months. At inclusion, patients will be counseled to follow a mild hypocaloric diet, to increase their exercise level, and to stop smoking (if smokers). Glucose/lipid parameters will be assessed at Baseline and every 6 months until the Month 30 visit. CIMT will be performed at Baseline and every 6 months until final assessment at Month 30 (primary endpoint).A post-treatment follow-up visit at Month 35 will allow the collection of all adverse events and cardiovascular outcomes occurring after last study drug administration

Enrollment

661 patients

Sex

All

Ages

55+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Written and signed informed consent
Age greater than or equal to 55 years
Abdominal obesity defined by waist circumference > 88 cm (35 inches) in women and > 102 cm (40 inches) in men
Metabolic syndrome diagnosed on the basis of at least two of the following additional risk factors:
1. Triglyceride level equal to or greater than 150 mg/dL
2. HDL cholesterol less than 40 mg/dL in men or 50 mg/dL in women
3. Fasting glucose of equal to or greater than 110 mg/dL
4. High blood pressure defined as equal to or greater than 140 mmHg systolic and/or equal to or greater than 90 mmHg diastolic at screening visit or current treatment by antihypertensive medication.
Ultrasonographic evidence at Screening quantitative B-mode ultrasound imaging of a minimal CIMT measurement of greater than or equal to 0.7 mm in either of the far walls of the common carotid artery, and maximal CIMT measurement less than 3 mm in any carotid artery segment.
All 6 carotid artery segments must have ultrasound images for all CIMT measurements
Screening CIMT recording deemed to be of acceptable CIMT image quality, and demonstrating adherence to the CIMT interrogation protocol, as determined by the Imaging Core Laboratory's assessment.

Exclusion criteria

History of very low calorie diet or surgical procedures for weight loss within 6 months prior to screening visit
Obesity of known endocrine origin
Uncontrolled diabetes, i.e. with HbA1c > 10%
Anticipated survival less than 27 months
Presence of any severe medical or psychological condition, that in the opinion of the Investigator, would compromise the subject's safety or successful participation in the study
Presence of any other condition (e.g. geographic, social, or other), actual or anticipated, that the Investigator feels would restrict or limit the subject's participation for the duration of the study
Receipt of any investigational treatment (drug or device) within 30 days prior to Screening
Previous participation in a rimonabant study
Total occlusion of any carotid artery segment
Previous history of carotid intervention
Patient considered at high risk of carotid intervention during the next 27 months