assessment of the safety and effect of sar425899 versus placebo for the treatment of non-alcoholic fatty liver disease

Conditions: Non-alcoholic Steatohepatitis; Type 2 Diabetes Mellitus

Summary: primary objective: - to evaluate the dose response relationship of sar425899 compared to placebo on resolution of non-alcoholic steatohepatitis (nash) with no worsening of fibrosis in diabetic and non-diabetic patients with histopathologically-confirmed nash. secondary objectives: * to assess the effect of sar425899 on overall non-alcoholic fatty liver disease (nafld) activity score (nas), individual components of nas (steatosis, hepatocyte ballooning, and lobular inflammation), and fibrosis score. * to assess to the effect of sar425899 on mri-pdff (magnetic resonance imaging-determined proton density fat fraction) derived parameters (total liver fat, liver volume, and fractional liver fat content). * to assess the effect of sar425889 on body weight and waist/hip circumference ratio. * to assess sar425899 pharmacokinetics. * to assess safety and tolerability of sar425899.

study duration per participant will be approximately 64 weeks, consisting of up to 8 weeks screening plus 52 weeks treatment and 4 weeks post treatment follow-up.

Eligibility criteria:
inclusion criteria : * non-diabetic or type 2 diabetes mellitus with confirmed non-alcoholic steatohepatitis. * non-alcoholic fatty liver disease (nafld) activity score (nas) \>=4 with each of its components \>=1. * patients without type 2 diabetes determined by hba1c (glycated hemoglobin) \<6.5% and fasting plasma glucose (fpg) \<7.0 mmol/l (\<126 mg/dl). * stable glycemic control (hba1c \<9.0%) and metabolic disorders managed with diet/exercise and/or stable dose metformin and/or sulphonylureas for at least 3 months prior to screening (type 2 diabetes patients). * signed written informed consent form. exclusion criteria: * diagnosis of type 1 diabetes mellitus. * previous insulin use or use of insulin within the last 6 months, except for episode(s) of short-term treatment (\<15 consecutive days) due to intercurrent illness. * body mass index (bmi) \ 45.0 kg/m2. * current participation in organized diet/weight reduction program or clinical trial of weight control (within the last 3 months prior to screening), or weight loss attempt, plans for major changes in physical activities or significant change in body weight in the 2 months prior to screening (significant change in body weight is defined as \>=5% self-reported change within 6 months prior to randomization if a pre-existing liver biopsy sample was collected prior to screening period. * current treatment with glucose-lowering agent(s) other than metformin or sulphonylureas, weight loss drugs including orlistat, systemic steroids, methotrexate, amiodarone, or vitamin e. * alcoholism (past or present) and/or average alcohol consumption per week \>21 units (210 g) for males, \>14 units (140 g) for females within the last 5 years. * poorly controlled hypertension (resting systolic blood pressure (sbp) \>160 mm hg and/or resting diastolic blood pressure (dbp) \>95 mm hg) at screening. * some liver diseases, pancreatic disease, liver transplantation and types of cancer. * pregnant or breast-feeding women. * women of childbearing potential (wocbp) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. * male subjects, whose partners are able to become pregnant, who do not accept to use a condom during sexual intercourse from study inclusion up to 3 months after last dosing; or who are planning to donate sperm from study inclusion up to 3 months after last dosing. * patients with coronary, carotid, or peripheral artery revascularization procedures planned during the screening or treatment phases of the protocol. * patients with unstable heart conditions. the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.