Clinical trial NCT00405808: Rimonabant in Abdominally Obese Patients With Impaired Fasting Blood Glucose
Official title: A Pan-European Randomized, Parallel Group, Two-arm Placebo-controlled, Double-blind Multicenter Study of Rimonabant 20mg Once Daily in the Treatment of Abdominally Obese Patients With Impaired Fasting Blood Glucose With or Without Other Comorbidities
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Obesity
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-11-30
Enrollment: 2666
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary objective:

To determine the effect of Rimonabant 20mg on the co-primary endpoint including Fasting Plasma Glucose (FPG), HDL-Cholesterol (HDL-C) and triglyceride (TG) levels over a period of 12 months when prescribed with a mild hypocaloric diet in abdominally obese patients with impaired fasting blood glucose and with or without associated comorbidities.

Main Secondary objectives:

To determine the effect of 12 months Rimonabant treatment versus placebo on changes in waist circumference (WC), body weight, glycemic parameters and lipid parameters.

To assess the safety of 12 months Rimonabant treatment versus placebo in these patients.


Eligibility criteria: Inclusion Criteria:

* BMI ≥ 30Kg/m², or \> 27kg/m² if associated with risk factor(s) such as dyslipidemia, and \< 40kg/m²,
* Waist Circumference \> 88 cm in women; \> 102 cm in men,
* Confirmed (by at least 2 measurements) impaired Fasting Plasma Glucose (FPG ≥ 100 mg/dl (5.6 mmol/L) and \< 126 mg/dl (7.0 mmol/L) in non diabetic patients,
* LDL cholesterol up to 155 mg/dl (4.00 mmol/L) including patients on a stable dose of statin therapy for at least 8 weeks prior to screening,
* Current treatment with statins and/or ezetimibe and/or antihypertensive therapy must be at fixed and stable dose for at least 8 weeks prior to screening visit,
* Patients, who are willing and in the opinion of the Investigator safely assumed to remain on stable and fixed doses of antihypertensive, and/or statins and/or ezetimibe without adding additional medications or changing current treatment for the duration of the trial.

Exclusion Criteria:

* Pregnant or breast-feeding women, or women planning to become pregnant or breastfeed (excluded by pregnancy test),
* Absence of medically approved contraceptive methods for female of childbearing potential,
* History of very low-calorie diet within 3 months prior to screening visit (lower than 1200 Kcal/day),
* Weight change \> 5 kg within 3 months prior to screening visit,
* History of surgical procedures for weight loss (e.g., stomach stapling, bypass),
* History of bulimia or anorexia nervosa as per DSM-IV criteria,
* Presence of any clinically significant endocrine disease according to the investigator, in particular known abnormal TSH and free T4 blood level (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),
* Established type 1 or 2 diabetes treated, or with at least 2 measures of fasting blood glucose ≥ 126 mg/dl /L,
* Triglyceride level \> 400 mg/dL (4.52 mmol),
* Systolic blood pressure \> 160 mm Hg or diastolic blood pressure \>100 mmHg at screening visit,
* Known severe renal dysfunction (creatinine clearance \< 30 ml/min) or nephrotic syndrome or urinalysis (performed at screening by dipstick) showing 2+ or more protein,
* Known severe hepatic impairment or AST and/or ALT \> 3 times the upper limit of normal at screening,
* Presence of any condition (medical, including clinically significant abnormal laboratory tests, psychological, social or geographical) actual or anticipated that the investigator feels would compromise the patient's safety or limit his/her successful participation to the study. In particular :

  * Cardiac abnormalities: cardiac failure status NYHA III or IV, relevant acute abnormal finding seen on ECG at screening or within 6 months before screening,
  * Any current malignancy or any cancer within the past five years (except adequately treated basal cell skin cancer or cervix carcinoma in situ),
  * Significant haematology abnormalities (haemoglobin \< 100 g/L and/or neutrophils \< 1.5 G/L and/or platelets \< 100 G/L),
  * Acute psychiatric disorders or mental condition which could interfere with the patient's compliance or safe participation in the study,
  * Patient treated for epilepsy,
* Ongoing major depressive illness,
* Uncontrolled psychiatric illness,
* History of alcohol or other substance abuse,
* Hypersensitivity /intolerance to the active substance or to any of the excipients such as lactose,
* Administration of any investigational treatment (drug or device) within 30 days prior to screening,
* Previous participation in a Rimonabant study or previous administration of Rimonabant,
* Administration of any of the following within 3 months prior to screening visit:

  1. Anti obesity drugs (eg, sibutramine, orlistat),
  2. Other drugs for weight reduction (phentermine, amphetamines),
  3. Herbal preparations for weight reduction,
  4. Nicotinic acid, fibrates or bile acid sequestrants ,
  5. Prolonged use (more than one week) of systemic corticosteroids, neuroleptics.
  6. Omega-3 fatty acid approved medication
* Ongoing antidepressive treatment(including bupropion)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Mean change in the co-primary endpoint : FPG, HDL-C and triglyceride levels.
timeFrame: From baseline to end of treatment
Secondary outcomes:
measure: Waist circumference and body weight
timeFrame: At each visit
measure: Glycemic parameters (FPG, fasting insulinemia, HbA1c), lipid parameters (Total Cholesterol, HDL-C, LDL-C, triglyceride levels), inflammatory parameter (Hs-CRP),
timeFrame: All these laboratory parameters will be measured prior to baseline, month 3, month 6 and month 12.
measure: Quality of life (IWQOL questionnaire completion)
timeFrame: At baseline, month 3, month 6, month 9 and month 12
measure: Incidence of adverse events in each group, including neuro-psychiatric adverse events
timeFrame: From the signature of the ICF to the end of the study
measure: Standard laboratory assessments
timeFrame: Prior to baseline and month 12
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Sofia
country: Bulgaria
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: Sanofi-Aventis Administrative Office
city: Cairo
country: Egypt
facility: Sanofi-Aventis Administrative Office
city: Helsinki
country: Finland
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Kallithea
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Dublin
country: Ireland
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Milan
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Vilnius
country: Lithuania
facility: Sanofi-Aventis Administrative Office
city: Luxembourg
country: Luxembourg
facility: Sanofi-Aventis Administrative Office
city: Col. Coyoacan
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Lysaker
country: Norway
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Bratislava
country: Slovakia
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Valérie Pilorget, MD
role: STUDY_DIRECTOR
References: