High Density Lipoprotein Turnover

Obesity Clinical Trial

Official title:

A Randomized, Double-blind, Two Arm, Parallel, Placebo Controlled Study of Rimonabant 20 mg Effect on High Density Lipoprotein Kinetics in Patients With Abdominal Obesity and Additional Cardiometabolic Risk Factors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00408148
• Other study ID #: RIMON_C_01346
• Secondary ID: EUDRACT # : 2006
• Status: Terminated
• Phase: Phase 3
• First received: December 5, 2006
• Last updated: December 9, 2010
• Start date: October 2006
• Est. completion date: December 2008

Study information

• Verified date: December 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Ethics Committee
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 64
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Placebo
Undistinguishable placebo tablets
• Rimonabant
White film-coated, for oral administration containing 20 mg of active rimonabant

Locations

Country	Name	City	State
Australia	Sanofi-Aventis Administrative Office	North Ryde
Finland	Sanofi-Aventis Administrative Office	Helsinki
France	Sanofi-Aventis Administrative Office	Paris
United Kingdom	Sanofi-Aventis Administrative Office	Guildford

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Australia,  Finland,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The fractional catabolic rate (FCR) of HDL ApoA-I		After 12 months of treatment.	No
Secondary	Production Rate (PR) of HDL ApoA-I and A-II, (FCR) of HDL ApoA-II		All across the study	No
Secondary	PR and FCR of VLDL1 and VLDL2 Apo B, VLDL1 and VLDL2 TG, IDL Apo B and LDL Apo B		All across the study	No
Secondary	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	No
Secondary	Variation in Glucose, insulin, HbA1c, leptin, adiponectin		All across the study	No
Secondary	Variation in hs-CRP, TNF-alpha, CETP, PLTP and LCAT activities, lipoprotein and hepatic lipase activities in post-heparin plasma		All across the study	No
Secondary	Variation in whole body fat		All across the study	No
Secondary	Variation in abdominal sub-cutaneous and visceral fat		All across the study	No
Secondary	Variation in liver fat		All across the study	No
Secondary	Variation in blood pressure		All across the study	No
Secondary	Variation in body weight, waist circumference, waist/hip ratio		From the beginning to the end of the study	No
Secondary	CE/TG ratio in HDL		All across the study	No
Secondary	Adverse events		From the beginning to the end of the study	Yes