High Density Lipoprotein Turnover

Sanofi

Status and phase

Terminated

Phase 3

Conditions

Obesity

Treatments

Drug: Rimonabant

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT00408148

EUDRACT # : 2006-001716-71

RIMON_C_01346

Details and patient eligibility

About

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

Enrollment

64 patients

Sex

All

Ages

35 to 65 years old

Volunteers

No Healthy Volunteers

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