Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model

Summary

The purpose of this study is to assess the effect of the anti-hepcidin Spiegelmer NOX-H94 on iron homeostasis during systemic inflammation induced by endotoxin. In the human endotoxemia model, intravenously administered lipopolysaccharide elicits an inflammatory response with release of pro-inflammatory cytokines, such as IL-6 and TNF-alfa, with subsequent induction of hepcidin. As a consequence of hepcidin induction, serum iron concentrations decrease. This study in healthy subjects investigates the capacity of NOX-H94 to inactivate hepcidin and to prevent serum iron decrease in a pathophysiological model prior to studying the efficacy of NOX-H94 in patients with anemia of chronic disease.

Timeline

Start

2012-01

Primary completion

2012-03

Completion

2012-04

Outcome

Met primary endpoint

paper in lexaptepid-treated subjects compared with a decrease of 8.3 ± 9.0 µmol/L in controls (P < .0001). PMID 25163699 ↗

Publications

• van Eijk LT, John AS, Schwoebel F, Summo L, Vauleon S, Zollner S, Laarakkers CM, Kox M, van der Hoeven JG, Swinkels DW, Riecke K, Pickkers P. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood. 2014 Oct 23;124(17):2643-6. doi: 10.1182/blood-2014-03-559484. Epub 2014 Aug 27.

Drugs

Indications