High Density Lipoprotein Turnover
High Density Lipoprotein Turnover
The objective of the study is to evaluate the effect of Rimonabant 20mg in comparison to
 placebo, on HDL and VLDL lipoprotein kinetics, over a 12 months period.

 Primary objectives:

 -  To assess effect of Rimonabant on HDL ApoA-I fractional catabolic rate (FCR).

 Secondary objectives:

 -  To assess effect of Rimonabant on HDL ApoA-I production rate (PR) and on other
 lipoprotein kinetics.

 -  To assess effect of Rimonabant on lipids, glycemic and inflammatory parameters

 -  To assess effect of Rimonabant on body composition

 -  To assess safety of Rimonabant
Inclusion Criteria:

 -  Abdominally obese patients with additional cardiometabolic risk factors

 -  Females must be post-menopausal

 -  BMI > 27 kg/m² and < 40 kg/m²

 -  Men or women with abdominal obesity according to NCEP/ATPIII criteria: Waist
 Circumference > 88 cm in women; > 102 cm in men

 -  With at least one lipid abnormality defined as:

 -  Fasting Triglycerides level > 1.7 mmol/L (150 mg/dL) and < 4.5 mmol/L (400 mg/dL)

 -  HDL < 1.03 mmol/L (40 mg/dL) in men and < 1.29 mmol/L (50 mg/dL) in women

 Exclusion Criteria:

 -  HDL ≤ 0.60 mmol/L (23 mg/dl)

 -  Plasma LDL-Cholesterol > 155 mg/dl (4.00 mmol/L) or total cholesterol 250 mg/dl (>
 6.5mmol/L) or genetic hyperlipidaemia

 -  Fasting triglycerides > 400 mg/dL (4.5 mmol/L)

 -  Known heterozygous or homozygous familial hypercholesterolaemia or know type III
 hyperlipoproteinaemia (familial dysbetalipoproteinaemia)

 -  ApoE2/E2 homozygosity, Apo E4/E4 homozygosity

 -  Type 2 diabetes treated with oral agents and/or insulin

 -  Diet treated type 2 diabetic patients with HbA1c ≥ 7%

 -  History of cardio vascular disease

 -  Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg.

 -  Very low-calorie diet (1200 calories a day or less) or history of surgical procedures
 for weight loss (e.g., stomach stapling, bypass)

 -  Body weight fluctuation > 5 Kg during the previous 3 months

 -  History of bulimia or anorexia nervosa by DSM-IV criteria

 -  Presence of any clinically significant endocrine disease according to the
 investigator, Cushing syndrome, obesity secondary to hypothalamic/pituitary disorder.

 -  Abnormal TSH and free T4 at baseline (Patients treated with thyroid replacement
 therapy must be on fixed and stable dose for at least 3 months prior to screening and
 must be in euthyroïd status.)

 -  Severe hepatic impairment known by the investigator or AST or ALT > 3 times the ULN at
 screening.

 -  Known severe renal dysfunction (creatinine clearance < 30 ml/min) or urine analysis
 (performed at screening by dipstick) showing 2+ or more protein

 -  Presence of any condition (medical, including clinically significant abnormal
 laboratory test, psychological, social or geographical) actual or anticipated that the
 investigator feels would compromise the patient safety or limit his/her successful
 participation to the study

 -  Patient treated for epilepsy

 -  Ongoing major depressive illness

 -  Uncontrolled psychiatric illness

 -  History of alcohol and/or drug abuse

 -  Smoker or smoking cessation within the past 3 months

 -  Marijuana or hashish users

 -  Previous participation in a Rimonabant study or to any other clinical trial within 4
 weeks to study start

 -  Hypersensitivity/intolerance to the active substance or to any of the excipients such
 as lactose

 -  Blood donation within the past 3 months prior to the study or planned during the study
 or within the 3 months from the study completing

 -  Recent history of active peptic ulcer

 -  Willebrand disease or other hemorrhagic diatheses

 -  Administration of any of the following within 3 months prior to screening visit and
 susceptible to be prescribed during the study treatment period:

 -  Lipid-lowering drugs intake

 -  Anti obesity drugs

 -  Other drugs for weight reduction (phentermine, amphetamines)

 -  Herbal preparations for weight reduction

 -  Other drugs known to affect lipid metabolism: retinoids, antiretroviral, estrogens and
 hormone replacement therapy, cyclosporine, glitazones, benfluorex, fish oils, plant
 sterols.

 -  Thiazids (including fixed combination) at daily dose higher than 12.5 mg

 -  Unselective beta-blockers

 -  Prolonged use (more than one week) of systemic corticosteroids, neuroleptics

 -  Anticoagulants

 -  Ongoing antidepressive treatment

 The above information is not intended to contain all considerations relevant to a patient's
 potential participation in a clinical trial.