Atherogenic dyslipidaemic patients with abdominal obesity MedDRA version: 9.1 Level: LLT Classification code 10058108 Term: Dyslipidaemia 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 if any- surgical removal of ovaries can be considered as “surgical menopause”)). 3) Aged from 18 to 75 years. 4) Waist circumference =102cm for male, = 88cm for female. 5) Atherogenic dislipidaemia* inadequately controlled despite Therapeutic Lifestyle Change (TLC) recommendations (diet and exercise). * (documented or highly probable at V1) 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)] 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). In addition to the above criteria, all of the following inclusion criteria must be fulfillled at V2 (or results of V2 labs): 8) 150= fasting TG = 600 mg/dL (1.69 = fasting TG = 6.78 mmol/L) at V2 9) Fasting HDL-C = 40 mg/dL (= 1.03 mmol/L) for male, HDL-C = 45 mg/dL (= 1.16 mmol/L) for female at V2 In addition to the above criteria, the following inclusion criterion must be fulfillled at V3: 10) Patient agrees to come to following visits and it is possible to schedule V4 and V5 inside the protocol specified range (14 days +/- 2 days between V3 and V4; 14 days +/- 2 days between V4 and V5). 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) 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) 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) Known homozygous familial hypercholesterolaemia or known Type III hyperlipoproteinaemia (familial dysbetalipoproteinaemia). 9) 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 10) 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 11) The Patient is a female of childbearing potential, is pregnant or lactating 12) 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. 13) Currently taking other investigational drugs or who have taken part in a clinical trial within the previous month prior to screening. 14) Known intolerance or contra-indication to the list of excipients of GFT505 (Gelatin, Lactose monohydrate, Titanium dioxide, Red Iron Oxide, Magnesium Stearate). 15) Patient not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force. 16) 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 V2 labs): 17) Uncontrolled hypothyroidism defined as TSH > 2 x the upper limit of normal (ULN) at V2 (thyroid dysfunction controlled for at least 6 months prior to screening is permitted). 18) Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance 180 µmol/L at V2). 19) Active liver disease or hepatic dysfunction***** as defined by elevations in liver enzymes: [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] >3 x the upper limit of normal (ULN) at V2, or [gamma glutamyltransferase (GGT) and alkaline phosphatases (ALP)] > 2 x the upper limit of normal (ULN) at V2. ***** Patients with NonAlcoholic SteatoHepatitis (NASH) will be allowed to participate in the study. 20) Unexplained serum creatine phosphokinase (CPK) > 3 x the upper limit of normal (ULN) at V2. Patients with a reason for CPK elevation may continue in screening and have the measurement repeated prior to randomization; a repeat CPK > 3 x ULN is exclusionary. In addition to the above criteria, the patient should not present any of the following exclusion criteria at V3: 21) Patient for whom the wash-out period of lipid-regulating drugs (f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the efficacy of GFT505 80mg in reducing LDL-C and non-HDL-C levels compared with placebo. To describe the changes in TG, HDL-C, LDL-C and non-HDL-C levels in the two groups. To describe the changes in other lipid parameters in the two groups. To describe the changes in inflammatory, oxidative stress and renal function markers in the two groups. To assess the plasma exposure of GFT505 after repeated once daily administrations of GFT505. ;Primary end point(s): Primary Endpoint: - Decrease in serum TG level from baseline to D28 (V5). - Increase in serum HDL-C level from baseline to D28 (V5). Secondary Endpoints: - Decrease in serum non-HDL-C and LDL-C levels from baseline to D28 (V5). - Changes from baseline to all study visits for other lipids (TG, HDL-C, Total Cholesterol, calculated VLDL-C) and special lipids (Apo AI, Apo AII, Apo B, Apo CIII, Apo CIII/B, Apo CIII-nonB, small dense LDL, remnants, FFA, Lp(a)). - Changes from baseline to D28 (V5) for inflammatory markers (hsCRP, TNF-alpha, IL-6, PAI-1, gene expression in leukocytes, amyloïd A serum, Lp-PLA2, ICAM, VCAM, adiponectin, leptin), for renal function markers (alpha-1 microglobulin, beta-NAG, N-Gal, albumin, creatinin, microscopic analysis and cystatin C), for oxidative stress markers [oxysterols, Vitamin E, HODE (hydroxyoctadecadienoic acid), isoprostans, trans isomers of arachidonic acid, oxidized LDL, paraoxanase]. - SAE, AE, physical examination, vital signs, medical history, ECG. - Haematology (haemoglobin, haematocrit, RBC, WBC and differential count, platelet counts, haptoglobin, prothrombin, reticulocytes count) and biochemical markers [insulin, fasting plasma glucose, creatinine, creatinine clearance, total proteins, albumin, electrolytes (sodium, potassium, chloride, calcium), uric acid, urea, AST, ALT, GGT, alkaline phosphatases, CPK, total and conjugated bilirubin, troponin I, fibrinogen, homocystein,TSH, HbA1c, fructosamin] and urinalysis. ;Main Objective: To e | — |
Countries
France
Outcome results
None listed