A randomized, placebo-controlled trial to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamics of a potent inhibitor of poly(ADP-ribose) polymerase (INO-1001) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: Results of the TIMI 37 trial

David A. Morrow*, Chaim M. Brickman, Sabina A. Murphy, Kenneth Baran, Ricardo Krakover, Harold Dauerman, Sujatha Kumar, Natanya Slomowitz, Laura Grip, Carolyn H. McCabe, Andrew L. Salzman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Reperfusion injury is a significant complication of the management of ST-elevation MI (STEMI). INO-1001 is a potent inhibitor of poly(ADP-ribose) polymerase (PARP), a mediator of oxidant-induced myocyte dysfunction during reperfusion. Methods & results: We assessed the safety and pharmacokinetics of INO-1001 in a randomized, placebo-controlled, single-blind, dose-escalating trial in 40 patients with STEMI undergoing primary percutaneous coronary intervention within 24 h of onset. INO-1001 was well-tolerated. A trend toward more frequent transaminitis was observed with 800 mg. Plasma from INO1001-treated patients reduced in vitro PARP activity >90% at all doses. Serial C-reactive protein and IL-6 levels showed a trend toward blunting of inflammation with INO-1001. The apparent median terminal half-life (t1/2) of INO-1001 was 7.5 (25th, 75th: 5.9, 10.2) h. Conclusions: The results from this first trial of INO-1001 in STEMI support future investigation of INO-1001 as a novel treatment for reperfusion injury.

Original languageEnglish
Pages (from-to)359-364
Number of pages6
JournalJournal of Thrombosis and Thrombolysis
Volume27
Issue number4
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Clinical trials
  • Myocardial infarction
  • Poly(ADP-ribose) polymerase
  • Reperfusion injury

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