In previous development efforts in unrelated indications such as myocardial infarction and sickle cell disease, P-188 NF has been used in over 2,500 subjects, including pediatric subjects, at intravenous doses two orders of magnitude higher than proposed for Carmeseal-MD. While at these very high doses a safety signal was observed in much older individuals with myocardial infarction and compromised renal function (elevated serum creatinine), this signal was not observed in much younger patients with normal renal function, even at very high doses. This strongly indicates safe use of P-188 NF at the dose and the route proposed for Carmeseal-MD.
High dose administration regimen in older patient with MI and compromised renal function that did show elevated serum creatinine levels in some subjects:
Collaborative Organization for RheothRx Evaluation (CORE). Effects of RheothRx on mortality, morbidity, left ventricular function and infarct size in patients with acute myocardial infarction. Circulation 1997; 96: 192-201.
High dose administration regimen that did not lead to elevated serum creatinine levels:
Adams-Graves P, Kedar A, Koshy M, Steinberg M, Veith R, Ward D, Crawford R, Edwards S, Busrack J, Emanuele M. RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study. Blood 1997; 90:2041-2046.
Additional human studies at high intravenous doses:
O’Keefe JH, Grines CL, DeWood MA, Schaer GL, Browne K, Magorien RD, et al. Poloxamer-188 as an adjunct to primary percutaneous transluminal coronary angioplasty for acute myocardial infarction. Am J Cardiol. 1996; 78:747-750.
Maynard C, Swenson R, Paris JA, Martin JS, Hallstrom AP, Cerqueira MD, et al. Randomized, controlled trial of RheothRx (poloxamer 188) in patients with suspected acute myocardial infarction. Am Heart J 1998; 135(5 Pt 1):797-804.
Schaer GL, Spaccavento LJ, Browne KF, et al. Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction: results of a randomized, double-blind, placebo-controlled trial. Circulation 1996; 94:298-307.