Clinical trial: the efficacy and safety of oral PF-03491390, a pancaspase inhibitor - a randomized placebo-controlled study in patients with chronic hepatitis C

Aliment Pharmacol Ther. 2010 May;31(9):969-78. doi: 10.1111/j.1365-2036.2010.04264.x. Epub 2010 Feb 16.


Background: Elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) reflect hepatocellular injury in patients with chronic hepatitis C virus (HCV). Increased apoptosis and activated caspases are present in these patients. PF-03491390 inhibits multiple caspases and lowers serum AST and ALT levels in patients with chronic liver diseases.

Aim: To determine if treatment with an oral pancaspase inhibitor could reduce serum AST and ALT in patients with HCV.

Methods: Double-blind, randomized, placebo-controlled, parallel-dose study in 204 patients treated with placebo or PF-03491390 (5, 25 or 50 mg) orally twice daily (b.d.) for up to 12 weeks. Serum AST and ALT were monitored weekly.

Results: Significant reductions in serum AST and ALT were observed within 1 week of initiating PF-03491390 in all treatment groups (P < 0.0001). These reductions in AST and ALT were maintained throughout the 12 week treatment period and returned to baseline levels when PF-03491390 was discontinued. Increasing the dose did not further lower AST or ALT. The most frequently reported adverse events were headache and fatigue.

Conclusion: PF-03491390 significantly reduced serum AST and ALT levels in patients with chronic HCV, and was well tolerated over 12 weeks.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Aspartate Aminotransferases / blood*
  • Caspase Inhibitors*
  • Double-Blind Method
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Pentanoic Acids / administration & dosage*
  • Pentanoic Acids / adverse effects
  • Treatment Outcome


  • 3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid
  • Caspase Inhibitors
  • Pentanoic Acids
  • Aspartate Aminotransferases
  • Alanine Transaminase