High Density Lipoprotein Turnover

This study has been terminated.
(Company decision has been taken in light of recent demands by certain national health authorities)
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00408148
First received: December 5, 2006
Last updated: December 9, 2010
Last verified: December 2010
  Purpose

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

Condition Intervention Phase
Obesity
Drug: Placebo
Drug: Rimonabant
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • The fractional catabolic rate (FCR) of HDL ApoA-I [ Time Frame: After 12 months of treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Production Rate (PR) of HDL ApoA-I and A-II, (FCR) of HDL ApoA-II [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • PR and FCR of VLDL1 and VLDL2 Apo B, VLDL1 and VLDL2 TG, IDL Apo B and LDL Apo B [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in Glucose, insulin, HbA1c, leptin, adiponectin [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in hs-CRP, TNF-alpha, CETP, PLTP and LCAT activities, lipoprotein and hepatic lipase activities in post-heparin plasma [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in whole body fat [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in abdominal sub-cutaneous and visceral fat [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in liver fat [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in blood pressure [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Variation in body weight, waist circumference, waist/hip ratio [ Time Frame: From the beginning to the end of the study ] [ Designated as safety issue: No ]
  • CE/TG ratio in HDL [ Time Frame: All across the study ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: From the beginning to the end of the study ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: October 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
Administration of one rimonabant placebo tablet once daily in the morning
Drug: Placebo
Undistinguishable placebo tablets
Experimental: 1
Administration of one tablet containing 20 mg of active rimonabant once daily in the morning
Drug: Rimonabant
White film-coated, for oral administration containing 20 mg of active rimonabant

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00408148

Locations
Australia
Sanofi-Aventis Administrative Office
North Ryde, Australia
Finland
Sanofi-Aventis Administrative Office
Helsinki, Finland
France
Sanofi-Aventis Administrative Office
Paris, France
United Kingdom
Sanofi-Aventis Administrative Office
Guildford, United Kingdom
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Valérie Pilorget Sanofi
  More Information

No publications provided

Responsible Party: Trial Transparency Team, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00408148     History of Changes
Other Study ID Numbers: RIMON_C_01346, EUDRACT # : 2006-001716-71
Study First Received: December 5, 2006
Last Updated: December 9, 2010
Health Authority: Finland: Ethics Committee

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Rimonabant
Cannabinoid Receptor Antagonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014