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

Phase 1

Completed

• Conditions: Anemia of Chronic Disease
• Interventions: Drug: NOX-H94; Drug: Placebo solution

• Registration Number: NCT01522794
• Lead Sponsor: TME Pharma AG

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-01-18
• Study First Submitted QC: 2012-01-27
• Study First Posted: 2012-02-01
• Primary Completion: 2012-03
• Study Completion: 2012-04
• Status Verified: 2014-11
• Last Update Submitted: 2014-11-07
• Last Update Posted: 2014-11-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NOX-H94	NOX-H94	Single dose of NOX-H94
Placebo	Placebo solution	Single dose of placebo control

Primary Outcome Measures

Name	Time	Method
serum iron	9 hours	Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics: AUC of NOX-H94	0-2 weeks
Pharmacokinetic profile of NOX-H94	12 time points over 2 Weeks	plasma concentration-time profile T0 to 2 weeks
Safety and tolerability	up to 2 Weeks	Safety and tolerability parameters will be evaluated along the entire study duration consisting of spontaneously reported adverse events, physical examination and vital signs, hematology and clinical chemistry laboratory examinations.
Pharmacokinetics: Clearance of NOX-H94	0-2 weeks
Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis	up to 2 Weeks	Change from baseline and group comparison (NOX-H94 vs. placebo) of: serum iron, transferrin saturation, ferritin
Effects of NOX-H94 on innate immune response	up to 2 weeks	To assess the effect of a single dose administration of NOX H94 on the innate immune response during experimental endotoxemia: TNF-α, IL-6, IL-1RA, IL-10
Pharmacokinetics: Cmax of NOX-H94	Day 1
Pharmacodynamics: effect of NOX-H94 on Red blood cell parameters	0- 2 weeks	Change versus baseline and group comparison: reticulocyte hemoglobin content, hemoglobin, mean cell volume, mean cell hemoglobin

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands