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Mehta G, Rousell S, Burgess G, et al. A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis. J Clin Exp Hepatol. 2017;8(3):224-234doi: 10.1016/j.jceh.2017.11.006.
Mehta, G., Rousell, S., Burgess, G., Morris, M., Wright, G., McPherson, S., Frenette, C., Cave, M., Hagerty, D. T., Spada, A., & Jalan, R. (2018). A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis. Journal of clinical and experimental hepatology, 8(3), 224-234. https://doi.org/10.1016/j.jceh.2017.11.006
Mehta, Gautam, et al. "A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis." Journal of clinical and experimental hepatology vol. 8,3 (2018): 224-234. doi: https://doi.org/10.1016/j.jceh.2017.11.006
Mehta G, Rousell S, Burgess G, Morris M, Wright G, McPherson S, Frenette C, Cave M, Hagerty DT, Spada A, Jalan R. A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis. J Clin Exp Hepatol. 2018 Sep;8(3):224-234. doi: 10.1016/j.jceh.2017.11.006. Epub 2017 Nov 22. PMID: 30302038; PMCID: PMC6175779.
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J Clin Exp Hepatol. 2018 Sep;8(3):224-234. doi: 10.1016/j.jceh.2017.11.006. Epub 2017 Nov 22.

A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis.

Journal of clinical and experimental hepatology

Gautam Mehta, Sam Rousell, Gary Burgess, Mark Morris, Gavin Wright, Stuart McPherson, Catherine Frenette, Matthew Cave, David T Hagerty, Alfred Spada, Rajiv Jalan

Affiliations

  1. Institute for Liver and Digestive Health, Royal Free Campus, UCL, London, UK.
  2. Clinical Outcomes Solutions, Folkestone, UK.
  3. Vectura Group PLC, Chippenham, UK.
  4. Department of Gastroenterology, Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon, UK.
  5. Liver Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  6. Department of Organ Transplantation, Scripps Green Hospital, San Diego, USA.
  7. Department of Medicine, University of Louisville School of Medicine, Louisville, USA.
  8. Conatus Pharmaceuticals Inc., San Diego, USA.

PMID: 30302038 PMCID: PMC6175779 DOI: 10.1016/j.jceh.2017.11.006

Abstract

BACKGROUND: Cirrhosis and acute-on-chronic liver failure (ACLF) are associated with systemic inflammation, and caspase-mediated hepatocyte cell death. Emricasan is a novel, pan-caspase inhibitor. Aims of this study were to assess the pharmacokinetics, pharmacodynamics, safety and clinical outcomes of emricasan in acute decompensation (AD) of cirrhosis.

METHODS: This was a phase 2, multicentre, double-blind, randomized trial. The primary objective was to evaluate the pharmacokinetics, pharmacodynamics and safety of emricasan in patients with cirrhosis presenting with AD and organ failure. AD was defined as an acute decompensating event ≤6 weeks' duration. Patients were randomized proportionately to emricasan 5 mg bid, emricasan 25 mg bid, emricasan 50 mg bid or placebo. Treatment was continued to 28 days, or voluntary discontinuation.

RESULTS: Twenty-three subjects were randomized, of whom 21 were dosed (placebo

CONCLUSION: This study demonstrates that emricasan is safe and well tolerated in advanced liver disease. However, this study fails to provide proof-of-concept support for caspase inhibition as a treatment strategy for ACLF.

TRIAL REGISTRATION: EudraCT 2012-004245-33.

Keywords: ACLF, acute-on-chronic liver failure; AD, acute decompensation; ALT, alanine aminotransferase; ANCOVA, analysis of covariance; AST, aspartate aminotransferase; Bid, Bis in die (twice a day); DL, decilitre; HCV, hepatitis C virus; INR, international normalised ratio; MELD, model for end-stage liver disease; Mg, milligrams; TNF, tumour necrosis factor; TRAIL, tumour necrosis factor-related apoptosis-inducing ligand; apoptosis; cell death; cirrhosis; liver failure

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