| Outcome Measures: |
Main Objective: Safety and tolerability assessment will be made by monitoring the subjects for adverse events and by interpreting the results of the ECGs, various laboratory tests (changes in ALT/AST) and the subjects?€? diaries.;Secondary Objective: ?€? Measurements of the hepatocellular lipid content (HCL)/composition and phosphorus metabolites by 3.0 and 7.0 Tesla Magnetic Resonance Spectroscopy (MRS) at 1H-MRS and 31P-MRS to investigate a lowering effect on HCL and possible changes in the liver cell metabolism. Comparison day 28 to baseline. <br>?€? Changes in oral glucose tolerance test (oGTT) using levels of glucose, insulin and c-peptide, FGF-19, GLP-1, DPP-4 as well as different measures of whole body insulin resistance (e.g. CLIX: serum creatinine, Gluc, C-Peptide) will be investigated prior and after administration of the study drug.<br>?€? Decrease of transaminases and parameters of cholestasis (ALT, AST, GGT, AP, Bilirubin)<br>?€? Potentially lowering of free serum cholesterol and triglycerols<br>?€? Reduction of body weight, BMI, waist-to-hip-ratio (WHR), ABSI (A body shape index)<br>?€? Plasma cholesterol lowering; <br>?€? FGF-19, Total bile acids reduction, <br><br>;Primary end point(s): Safety Endpoints:<br>?€? Number of AEs, SAEs, TEAE<br>?€? Changes in vital signs from baseline<br>?€? ECG-related safety endpoints:<br>o Occurrence of VES (determined by Holter-ECG)<br>o Change of QTc (derived from 12-lead ECG) from baseline <br>?€? Hepatological safety endpoints:<br>o Change of ALT, AST from baseline<br>o Change of Bilirubin from baseline<br>?€? Changes in other laboratory values (e.g. serum creatinine) from baseline<br>?€? Changes in concomitant medication<br>;Timepoint(s) of evaluation of this end point: 28 days post-baselineSecondary end point(s): Change in of hepatocellular lipid content (HCL; derived using MRS) from baseline to Day 28.<br>?€? Changes in glucose, insulin and C-peptid concentrations (derived using oral glucose tolerance test (oGTT)) from baseline to Day 28.<br>?€? Change in levels of transaminases and parameters of cholestasis (ALT, AST, GGT, AP, Bilirubin) from baseline<br>?€? Lowering of free serum cholesterol and triglycerides from baseline<br>?€? Changes in bile acid composition and lowering of total plasma bile acid pool from baseline<br>?€? Reduction of body weight, BMI, waist-to-hip-ratio (WHR), ABSI (A body shape index) baseline<br>?€? Changes in phagocytic function of Kupffer cells (KCs) and possible microcirculatory changes in the liver from baseline. Changes in other serum or plasma markers of liver inflammation and fibrotisation (CK-18, sCD163, Procollagen III peptide, Hyaluronic Acid, TIMP-1, alpha2-macroglobulin, haptoglobin, HRG-1 and others) from baseline<br>?€? Changes in bacterial translocation as evidenced by SLM-S test from baseline<br>;Timepoint(s) of evaluation of this end point: 28 days post-baseline
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