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

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: NOXXON Pharma AG

Criteria

Main Inclusion Criteria:

• BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg

• Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters

• Serum iron and red blood parameters Hb, MCV, ferritin, serum iron, and total iron binding capacity within reference range

Main Exclusion Criteria:

• Use of any medication, recreational drugs or anti-oxidant vitamin supplements within 7 days

• Use of caffeine, nicotine, or alcohol within 1 day

• Previous participation in a trial where LPS was administered

• Surgery or trauma with significant blood loss or blood donation within 3 months

• History, signs or symptoms of cardiovascular disease (vaso-vagal collapse or of orthostatic hypotension, Resting pulse rate ≤45 or ≥100/min, Hypertension, Hypotension, ECG conduction abnormalities)

• Renal impairment: plasma creatinine >120 µmol/L

• Liver function tests (alkaline phosphatase, AST, ALT and γ-GT) outside of the reference range or total bilirubin >20 µmol/L

• Hemoglobin or iron parameters (iron, transferring saturation, ferritin) outside of the reference ranges

• History of asthma

• Immuno-deficiency

• Positive test of HIV type 1/2 antibodies, HBs antigen, HBc antibodies and HCV antibodies unless antibody titer is induced by vaccination

• CRP > reference range or clinically significant acute illness, including infections, within 2 weeks

• Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration

• Known or suspected of not being able to comply with the trial protocol

• Inability to personally provide written informed consent and/or take part in the study