A phase 2, randomized, double‐blind, placebo‐controlled study of GS‐9450 in subjects with nonalcoholic steatohepatitis
dc.contributor.author | Ratziu, Vlad | en_US |
dc.contributor.author | Sheikh, Muhammad Y. | en_US |
dc.contributor.author | Sanyal, Arun J. | en_US |
dc.contributor.author | Lim, Joseph K. | en_US |
dc.contributor.author | Conjeevaram, Hari S. | en_US |
dc.contributor.author | Chalasani, Naga | en_US |
dc.contributor.author | Abdelmalek, Manal | en_US |
dc.contributor.author | Bakken, Anezi | en_US |
dc.contributor.author | Renou, Christophe | en_US |
dc.contributor.author | Palmer, Melissa | en_US |
dc.contributor.author | Levine, Robert A. | en_US |
dc.contributor.author | Bhandari, B. Raj | en_US |
dc.contributor.author | Cornpropst, Melanie | en_US |
dc.contributor.author | Liang, Wei | en_US |
dc.contributor.author | King, Benjamin | en_US |
dc.contributor.author | Mondou, Elsa | en_US |
dc.contributor.author | Rousseau, Franck S. | en_US |
dc.contributor.author | McHutchison, John | en_US |
dc.contributor.author | Chojkier, Mario | en_US |
dc.date.accessioned | 2012-03-16T15:54:48Z | |
dc.date.available | 2013-04-01T14:17:25Z | en_US |
dc.date.issued | 2012-02 | en_US |
dc.identifier.citation | Ratziu, Vlad; Sheikh, Muhammad Y.; Sanyal, Arun J.; Lim, Joseph K.; Conjeevaram, Hari; Chalasani, Naga; Abdelmalek, Manal; Bakken, Anezi; Renou, Christophe; Palmer, Melissa; Levine, Robert A.; Bhandari, B. Raj; Cornpropst, Melanie; Liang, Wei; King, Benjamin; Mondou, Elsa; Rousseau, Franck S.; McHutchison, John; Chojkier, Mario (2012). "A phase 2, randomized, double‐blind, placebo‐controlled study of GS‐9450 in subjects with nonalcoholic steatohepatitis ." Hepatology 55(2): 419-428. <http://hdl.handle.net/2027.42/90118> | en_US |
dc.identifier.issn | 0270-9139 | en_US |
dc.identifier.issn | 1527-3350 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/90118 | |
dc.description.abstract | In nonalcoholic steatohepatitis (NASH), the extent of hepatocyte apoptosis correlates with disease severity. Reducing hepatocyte apoptosis with the selective caspase inhibitor GS‐9450 has a potential for altering the course of the liver disease. In this phase 2, double‐blind study, 124 subjects with biopsy‐proven NASH were randomized to once‐daily placebo or 1, 5, 10, or 40 mg GS‐9450 for 4 weeks. Absolute and percent changes from baseline in ALT levels, AST levels, and caspase‐3–cleaved cytokeratin (CK)‐18 fragments at week 4 were assessed by an analysis of covariance model with adjustment for baseline values. In the 40‐mg group, mean (SD) ALT decreased by 47 (43) U/L from baseline to week 4 ( P < 0.0001 versus placebo), and the proportion of subjects with normal ALT increased from 0% to 35% at week 4. In the 40‐mg group, mean AST decreased by 13 U/L from baseline (not significant), and the proportion with normal AST increased from 20% at baseline to 48% at week 4. By week 4, mean CK‐18 fragment levels had decreased to 393 (723) U/L in the GS‐9450 10‐mg group and 125 (212) U/L in the 40‐mg group, but these reductions were not statistically significant. No serious adverse events were reported during treatment, and the percentage of subjects with at least one treatment‐emergent grade 3 or 4 laboratory abnormality ranged from 11.5% to 17% across the GS‐9450 treatment groups versus 35% in the placebo group. Conclusion : GS‐9450 treatment induced significant reductions in ALT levels in NASH patients. Reductions in CK‐18 fragment levels also occurred, although they were not statistically significant. At appropriate therapeutic indices, selective caspase inhibitors may be a promising treatment option in patients with NASH. (H epatology 2012) | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.title | A phase 2, randomized, double‐blind, placebo‐controlled study of GS‐9450 in subjects with nonalcoholic steatohepatitis | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan Medical Center, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Delta Research Partners, LLC, Monroe, LA | en_US |
dc.contributor.affiliationother | Université Pierre et Marie Curie, Hôpital Pitié‐Salpêtrière, Paris, France | en_US |
dc.contributor.affiliationother | University of California at San Francisco, Fresno, CA | en_US |
dc.contributor.affiliationother | Virginia Commonwealth University School of Medicine, Richmond, VA | en_US |
dc.contributor.affiliationother | Yale Liver Center, Yale University School of Medicine, New Haven, CT | en_US |
dc.contributor.affiliationother | Indiana University School of Medicine, Indianapolis, IN | en_US |
dc.contributor.affiliationother | Department of Medicine, Duke University Medical Center, Durham, NC | en_US |
dc.contributor.affiliationother | Center for Digestive Health, Troy, MI | en_US |
dc.contributor.affiliationother | Hôpital de Jour, Centre Hospitalier d'Hyères, Hyères, France | en_US |
dc.contributor.affiliationother | NYU Hepatology Associates, Plainview, NY | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, State University of New York Upstate Medical University, Syracuse, NY | en_US |
dc.contributor.affiliationother | Gilead Sciences, Inc., Foster City, CA | en_US |
dc.contributor.affiliationother | University of California, San Diego, San Diego, CA | en_US |
dc.contributor.affiliationother | Université Pierre et Marie Curie, Centre Hospitalier Pitié Salpétrière, 47‐83 Boulevard de l'Hôpital, 75013 Paris, France | en_US |
dc.identifier.pmid | 22006541 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/90118/1/24747_ftp.pdf | |
dc.identifier.doi | 10.1002/hep.24747 | en_US |
dc.identifier.source | Hepatology | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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