Patients with insulin resistance and abdominal obesity MedDRA version: 12.1 Level: LLT Classification code 10036481 Term: Pre-diabetes MedDRA version: 12.1 Level: LLT Classification code 10059179 Term: Abdominal obesity MedDRA version: 12.1 Level: LLT Classification code 10022489 Term: Insulin resistance
Conditions
Sponsors
GENFIT
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent prior to enrolment. 2. Male. 3. Aged from 18 to 75 years. 4. Waist circumference =94cm. 5. BMI = 45kg/m2 6. HOMA-IR > 3 7. Patients with diet and physical exercise stable within 3 months prior to screening. 8. Non-hypertensive or patient taking antihypertensive medication (except non-permitted medication) maintained at a stable dose for 2 months at least prior to screening (and the stable dose can be maintained throughout the study). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Blood Pressure > 160 / 95 mmHg. 2. Known Heart Failure (Grade I to IV of NYHA classification). 3. Patients who had an acute cardiovascular episode within 6 months prior to the start of the trial, or with a history of coronary angioplasty, stroke, TIA (Transient Ischemic Attack)], Coronary Heart Disease (Angina pectoris, history of myocardial infarction, revascularisation procedures) 4. Diabetes mellitus type 1 or 2. 5. Historical of bariatric surgery 6. Evidence of any other unstable or untreated clinically significant immunological, neoplastic, endocrine, haematological, gastrointestinal, hepatic, neurological or psychiatric abnormalities or medical disease. 7. Patients who have serious or unstable medical or psychological conditions which, in the opinion of the Investigator, would lead the patient to be non-compliant or uncooperative during the study or would compromise the patient's safety or successful participation in the study 8. Known intolerance or contra-indication to the list of excipients of GFT505 (Gelatin, Lactose monohydrate, Titanium dioxide, Red Iron Oxide, Magnesium Stearate). 9. Known alcohol and/or any other drug abuse or dependence. Alcohol consumption of more than 3 alcoholic beverages per day is considered abusive. One alcoholic beverage is defined as 30 mL distilled spirits, 120 mL wine, or 330 mL beer. 10. Patients who smoke more than 10 cigarettes per day 11. Patients who have donated blood or blood products within the previous month prior to screening or who plan to donate blood or blood products at any time during the trial and in the 3 months following the end of the study. 12. Patient not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force. 13. Patient who cannot be contacted in case of emergency. 14. Any medication that may interfere with study medication absorption, distribution, metabolism or excretion or could lead to induction or inhibition of microsomial enzymes within 3 months prior to the screening day. 15. Patient who has taken any non-permitted medication. 16. Patient treated with a lipid-decreasing medication (apart from statins and ezetimibe) - Note that : Patients using statins (except fluvastatin) and/or ezetimibe before the inclusion may participate if the dose is constant and stable at least for 3 months prior screening and remains constant during the study. 17. Currently taking other investigational drugs or who have taken part in a clinical trial within the previous month prior to screening. 18. A fasting plasma triglycerides concentration>400mg/dL or a plasma LDL-c concentration>220mg/dL 19. Uncontrolled hypothyroidism defined as TSH > 2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted. 20. Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance 180 µmol/L). 21. Active liver disease or hepatic dysfunction as defined by elevations in liver enzymes: [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT)>3X the upper limit of normal (ULN). 22. Unexplained serum creatine phosphokinase (CPK) > 2X the upper limit of normal (ULN). Patients with a reason for CPK elevation may continue in screening and have the measurement repeated prior to randomisation; a repeat CPK > 2X ULN is exclusionary.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate in each patient the differences in GIR (Glucose Infusion Rate) & HGP (Hepatic Glucose Production), measured at the end of 8 weeks treatment periods with GFT505 (80 mg/d per os) or placebo according to a cross-over design. - To compare the changes from baseline to endpoint in GIR (Glucose Infusion Rate) & HGP (Hepatic Glucose Production). The same baseline will be used for the 2 periods.;Secondary Objective: - To compare the changes from baseline, achieved after 8-week treatment with GFT505 80mg/d versus placebo in: - Glucose homeostasis - Lipid metabolism - Inflammatory markers and others parameters - Liver function (Non-Alcoholic Fatty Liver Disease markers) - To compare the changes from baseline in parameters associated with the glucose clamp procedures (GIR, HGP…) achieved at the end of the first 8-week treatment period in the two groups. - To compare gene expression (insulin signaling, lipid and glucose metabolism) in muscular tissue biopsy collected at the end of the first treatment period in the two groups. - To assess the safety of once-a-day administrations of oral doses of GFT505 80mg during 8 weeks.;Primary end point(s): Primary Endpoint: - To evaluate in each patient the differences in GIR (Glucose Infusion Rate) & HGP (Hepatic Glucose Production), measured at the end of 8 weeks treatment periods with GFT505 (80 mg/d per os) or placebo according to a cross-over design. - To compare the changes from baseline to endpoint in GIR (Glucose Infusion Rate) & HGP (Hepatic Glucose Production). The baseline will be defined as the values of glucose clamp at V2. The same baseline will be used for the 2 periods. End-points will be defined as glucose clamp values at V4 for the first period and as glucose clamp values at V7 for the second period. Secondary Endpoints: - To evaluate in each patient the differences in other parameters measured during the glucose clamp procedures performed at the end of 8 we | — |
Countries
France
Outcome results
None listed