Aim: To gather evidence for the safety and tolerability of an oral silybin-phosphatidylcholine phytosome (SiliphosTM) at three doses: 360 mg tid, 720 mg tid, and 1080 mg tid in subjects with chronic hepatitis C with stages II, III and IV of liver fibrosis and who are non-responders to or poor candidates for interferon-based regimens and have persistently abnormal serum alanine aminotransferase (ALT) levels.Study Design: This is a phase I/II open label, randomized dose-finding study. It has three arms corresponding to three different SiliphosTM doses: 360-mg tid, 720-mg tid, and 1080-mg tid. Each arm has 12 subjects diagnosed with chronic hepatitis C. Each arm is stratified to four subjects with fibrosis stage II (periportal fibrosis), four subjects with fibrosis stage III (bridging fibrosis) and four subjects with fibrosis stage IV (compensate cirrhosis). Each stratified subject is randomized to one of the three dose arms. The treatment duration is 12 weeks. Subjects will be followed for an additional four weeks after treatment cessation to assess residual effects of measured parameters.Endpoints: The primary endpoint is to gather evidence for dose-dependent safety and tolerability of SiliphosTM at the three proposed doses in the study cohort. Safety and tolerability will be measured by number and severity of Adverse Events (AEs) that occur during 12 weeks of treatment and four weeks of follow-up. Secondary endpoints include changes during treatment and follow-up in serum alanine aminotransferase (ALT), transferrin iron saturation, transferrin receptor, ferritin, hyaluronic acid, procollagen III peptide, transforming growth factot beta-1 and plasma chondrex (YLK-40) levels.
| Bares, Julie M; Berger, Jose; Nelson, James E et al. (2008) Silybin treatment is associated with reduction in serum ferritin in patients with chronic hepatitis C. J Clin Gastroenterol 42:937-44 |
