First clinical trial of a novel caspase inhibitor: anti-apoptotic caspase inhibitor, XXXX , improves liver enzymes.

@entity1 @entity32 @entity137 @entity6571 @entity409 @entity33144 @entity492 @entity3527 @entity493
OBJECTIVE: To evaluate the safety of @entity33144 , a novel anti-apoptotic pan-caspase inhibitor, administered in single and multiple ascending doses in normal volunteers and @entity1 with @entity409 . MATERIALS AND METHODS: @entity33144 was administered as a 30-minute intravenous infusion in rising doses to 3 groups: Group A, normal volunteers, given as a single infusion, Group B, normal volunteers, given q.i.d. for 7 days, Group C, @entity1 with @entity409 (elevated transaminases, @entity493 transaminase, ALT and @entity492 transaminase, @entity6571 ), given q.i.d. for 7 days. RESULTS: The drug was well tolerated up to 10 mg/kg/infusion for a single dose, and 1.5 mg/kg/infusion q.i.d. for 7 days, with the dose-limiting adverse event of @entity3527 or @entity32 at the site of the infusion. This @entity137 was predicted from animal studies. Clinically and statistically meaningful dose-related falls in transaminases were seen in all but 1 of the @entity409 @entity1 . Two-way ANOVA analyses of the changes for all the @entity33144 groups combined versus placebo were: ALT absolute change: p < 0.0001 and % change: p = 0.012, @entity6571 absolute and % changes: p < 0.0001. After discontinuation of the drug (after 7 days of dosing), the transaminases rapidly returned to the pre-treatment levels. CONCLUSIONS: Following intravenous administration of a novel anti-apoptotic caspase inhibitor, adverse events were mild-to-moderate in severity, resolved in a few days and did not result in any subject terminating treatment prematurely. The effects in @entity409 @entity1 appear to be consistent with both the administration and subsequent abrupt withdrawal of an effective hepatoprotective drug that delays cell death in hepatocytes.
