TY - JOUR
T1 - 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
T2 - Results of the TIMI 37 trial
AU - Morrow, David A.
AU - Brickman, Chaim M.
AU - Murphy, Sabina A.
AU - Baran, Kenneth
AU - Krakover, Ricardo
AU - Dauerman, Harold
AU - Kumar, Sujatha
AU - Slomowitz, Natanya
AU - Grip, Laura
AU - McCabe, Carolyn H.
AU - Salzman, Andrew L.
N1 - Funding Information:
Acknowledgments TIMI 37A was supported by the NIH R44 HL074684-01 and by Inotek Pharmaceuticals Corporation.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Clinical trials
KW - Myocardial infarction
KW - Poly(ADP-ribose) polymerase
KW - Reperfusion injury
UR - http://www.scopus.com/inward/record.url?scp=67349272283&partnerID=8YFLogxK
U2 - 10.1007/s11239-008-0230-1
DO - 10.1007/s11239-008-0230-1
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C2 - 18535785
AN - SCOPUS:67349272283
SN - 0929-5305
VL - 27
SP - 359
EP - 364
JO - Journal of Thrombosis and Thrombolysis
JF - Journal of Thrombosis and Thrombolysis
IS - 4
ER -