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

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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