patients presenting with impaired glucose tolerance and abdominal obesity MedDRA version: 9.1 Level: LLT Classification code 10036481 Term: Pre-diabetes MedDRA version: 9.1 Level: LLT Classification code 10059179 Term: Abdominal obesity
Conditions
Sponsors
GENFIT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrolment into the trial: 1) Provide written informed consent prior to enrolment. 2) Male or post-menopausal female (defined as >12 months since last menstrual period and with stable (at least 6 months prior to screening) and continuous Hormonal Replacement Therapy or surgical menopause). 3) Aged from 18 to 75 years. According to local regulations, Tunisian patients should be aged from 20 to 75 years. 4) Waist circumference =94cm for male, = 80cm for female. 5) Fasting Plasma Glucose (FPG) between 110* and 126 mg/dl (between 6.1 and 7.0 mmol/l) within 6 months prior to the screening visit (documented in the patient file), and/or analysed the day after visit V1 (B1 lab). * a tolerance of 10% for the lower limit is authorised. 6) Patients without previous experience of CVD**. ** Cardiovascular disease will be defined as: 1) Peripheral Artery Disease a) Lower limb [history of acute leg ischemia or clinical symptoms of arteriopathy (intermittent claudication within 6 months preceding the study)] b) Peripheral carotid artery disease [history of stroke, TIA (Transient Ischemic Attack)] c) Abdominal aortic aneurysm 2) Coronary Heart Disease (Angina pectoris, history of myocardial infarction, revascularisation procedures) 7) 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). 8) Sedentary habits (patients not exercising more than 2 hours per week and not having occupational activity necessitating physical efforts). 9) Patient agrees to come to following visits inside the protocol specified range In addition to the above criteria, all of the following inclusion criteria must be fulfilled at V2 (or results of B2 lab): 10) 2-hour glycaemia at OGTT* (2hr after a 75g oral glucose load) =140 mg/dL (7.8 mmol/l) at B2 lab, taken from blood sample within 7 days before V2. * a tolerance of 10% is authorized 11) Negative ECG stress test within the 12 months prior to the visit V1 (documented in the patient file) or performed between V1 and V2 visits, to exclude patients with contraindications to moderate-intensity exercise (underlying coronaropathy or arrythmmia). 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: Patients presenting with any of the following exclusion criteria will not be included in the trial: 1) Body Mass Index (BMI) = 40 kg/m². 2) Weight change (variation >5%) within 6 months at least prior to screening. 3) Known Heart Failure (Grade I to IV of NYHA classification). 4) Blood Pressure > 160 / 95 mmHg. 5) 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. 6) Known Type I or type II Diabetes Mellitus. 7) Evidence of any other unstable or untreated clinically significant immunological, neoplastic, endocrine, haematological, gastrointestinal, neurological or psychiatric abnormalities or medical disease. 8) Any serious medical condition that prevent participants from adhering to the protocol or performing the physical exercise test safely (ie. articular symptomatology or chronic respiratory disease) 9) Evidence of any acute and chronic inflammatory processes 10) Known homozygous familial hypercholesterolaemia or known Type III hyperlipoproteinaemia (familial dysbetalipoproteinaemia). 11) 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. 12) 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. 13) The Patient is a female of childbearing potential, is pregnant or lactating. 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) Patients having taken oral anti-diabetic drugs in the 3 months preceding randomisation visit. 16) Concomitant treatment with drugs known to affect plasma lipid levels and plasma glucose levels. 17) Currently taking other investigational drugs or who have taken part in a clinical trial within the previous month prior to screening. 18) Known intolerance or contra-indication to the list of excipients of GFT505 (Gelatin, Lactose monohydrate, Titanium dioxide, Red Iron Oxide, Magnesium Stearate). 19) Patient not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force. 20) Patient who cannot be contacted in case of emergency. In addition to the above criteria, the patient should not present any of the following exclusion criteria at V2 (or results of B1 and B2 lab): 21) Glycated haemoglobin (HbA1c) >7% 22) 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. 23) Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance 180 µmol/L). 24) 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), and [alkaline phosphatases (ALP)]>
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of GFT505 80mg compared with placebo in improving Oral Glucose Tolerance Test (OGTT), in patients with impaired glucose tolerance and abdominal obesity. To assess the tolerability and safety of once-a-day administrations of oral doses of GFT505 during 35 days. ;Secondary Objective: To evaluate the efficacy of GFT505 80mg compared with placebo in improving the VO2max. To describe the changes on others parameters measured during the physical exercise test (VCO2, RQ, lactate concentration...) To describe the changes of fasting glycaemia, insulinemia and HOMA index in the two groups. HOMA index is calculated as follow: [fasting serum glucose (mmol/l) X fasting insulin level (µunits/ml) /22,5]. To describe the changes in TG, HDL-C, LDL-C and non-HDL-C levels in the two groups. To describe the changes in inflammatory markers and others parameters, in the two groups. To describe the changes in the circulating shed membrane microparticles (MP) signature To describe the changes in pedometer measurements (number of daily steps) To assess the plasma exposure of GFT505 after repeated once daily administrations of GFT505 ;Primary end point(s): Primary Endpoint: - Change in plasma Glucose 2hr following oral glucose load from baseline (B2) to B4. Secondary Endpoints: - Change in VO2max at physical exercise test measured at baseline (V2) and V4. - Changes on others parameters measured during the physical exercise test (VCO2, RQ, lactate concentration...) at baseline (V2) and V4. - Changes in OGTT parameters (insulin AUC, glucose AUC) measured at baseline (B2) and B4. - Changes in fasting glycaemia and insulinemia from baseline (B2) to B4. - Changes from baseline (B2) to B4 in HOMA index. - Number of daily steps covered by patients at baseline visit (V2) and V4, measured by a pedometer. - Changes from baseline (B2) to B4 in lipids (LDL-C, non-HDL-C,TG, HDL-C, Total Cholesterol, calculated VLDL-C) and special lipids (Apo AI, Apo AII, Apo B | — |
Countries
France
Outcome results
None listed