Obesity
Conditions
Brief summary
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
Interventions
DRUGPlacebo
Undistinguishable placebo tablets
DRUGRimonabant
White film-coated, for oral administration containing 20 mg of active rimonabant
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The fractional catabolic rate (FCR) of HDL ApoA-I | After 12 months of treatment. |
Secondary
| Measure | Time frame |
|---|---|
| PR and FCR of VLDL1 and VLDL2 Apo B, VLDL1 and VLDL2 TG, IDL Apo B and LDL Apo B | All across the study |
| Variation in ApoA-I, ApoA-II, Lp-AI, Lp-AII, pre-beta-HDL HDL2a, HDL2b, HDL3a, HDL3b, HDL3c, Apo B, Apo C III, TG, LDL-C, HDL-C levels | All across the study |
| Variation in Glucose, insulin, HbA1c, leptin, adiponectin | All across the study |
| Variation in hs-CRP, TNF-alpha, CETP, PLTP and LCAT activities, lipoprotein and hepatic lipase activities in post-heparin plasma | All across the study |
| Variation in whole body fat | All across the study |
| Production Rate (PR) of HDL ApoA-I and A-II, (FCR) of HDL ApoA-II | All across the study |
| Variation in liver fat | All across the study |
| Variation in blood pressure | All across the study |
| Variation in body weight, waist circumference, waist/hip ratio | From the beginning to the end of the study |
| CE/TG ratio in HDL | All across the study |
| Adverse events | From the beginning to the end of the study |
| Variation in abdominal sub-cutaneous and visceral fat | All across the study |
Countries
Australia, Finland, France, United Kingdom
Outcome results
None listed