High Density Lipoprotein Turnover

NCT00408148 | Terminated Phase 3

• 2 other identifiers: RIMON_C_01346EUDRACT # : 2006-001716-71
• Study Type: interventional
• Target: 64
• Locations: 4 countries
• Sites: 4

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

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• The fractional catabolic rate (FCR) of HDL ApoA-I

  After 12 months of treatment.

Secondary Outcomes (12)

• Production Rate (PR) of HDL ApoA-I and A-II, (FCR) of HDL ApoA-II

  All across the study

• 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

Study Arms (2)

2

PLACEBO COMPARATOR

Administration of one rimonabant placebo tablet once daily in the morning

Drug: Placebo

1

EXPERIMENTAL

Administration of one tablet containing 20 mg of active rimonabant once daily in the morning

Drug: Rimonabant

Interventions

Placebo DRUG

Undistinguishable placebo tablets

2

Rimonabant DRUG

White film-coated, for oral administration containing 20 mg of active rimonabant

1

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Sanofi-Aventis Administrative Office

North Ryde, Australia

Location

Sanofi-Aventis Administrative Office

Helsinki, Finland

Location

Sanofi-Aventis Administrative Office

Paris, France

Location

Sanofi-Aventis Administrative Office

Guildford, United Kingdom

Location

Related Publications (1)

• Verges B, Adiels M, Boren J, Barrett PH, Watts GF, Chan D, Duvillard L, Soderlund S, Matikainen N, Kahri J, Robin I, Taskinen MR. Interrelationships between the kinetics of VLDL subspecies and HDL catabolism in abdominal obesity: a multicenter tracer kinetic study. J Clin Endocrinol Metab. 2014 Nov;99(11):4281-90. doi: 10.1210/jc.2014-2365. Epub 2014 Jul 31.

  PMID: 25077901 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Rimonabant

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines

Study Officials

• Valérie Pilorget

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 5, 2006
• First Posted: December 6, 2006
• Study Start: October 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: December 10, 2010

Record last verified: 2010-12

Locations

FR (1); FI (1); GB (1); AU (1)