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

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ClinicalTrials.gov Identifier: NCT01522794
Recruitment Status : Completed
First Posted : February 1, 2012
Last Update Posted : November 10, 2014
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Anemia of Chronic Disease Drug: NOX-H94 Drug: Placebo solution Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Placebo Controlled PK/PD Study on the Effects of a Single Intravenous Dose of NOX-H94 on Serum Iron During Experimental Human Endotoxemia
Study Start Date : January 2012
Actual Primary Completion Date : March 2012
Actual Study Completion Date : April 2012

Arm Intervention/treatment
Experimental: NOX-H94
Single dose of NOX-H94
Drug: NOX-H94
single i.v. infusion
Other Name: lexaptepid pegol

Placebo Comparator: Placebo
Single dose of placebo control
Drug: Placebo solution
single i.v. infusion

Primary Outcome Measures :
  1. serum iron [ Time Frame: 9 hours ]
    Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo

Secondary Outcome Measures :
  1. Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis [ Time Frame: up to 2 Weeks ]

    Change from baseline and group comparison (NOX-H94 vs. placebo) of:

    serum iron, transferrin saturation, ferritin

  2. Pharmacokinetic profile of NOX-H94 [ Time Frame: 12 time points over 2 Weeks ]
    plasma concentration-time profile T0 to 2 weeks

  3. Safety and tolerability [ Time Frame: 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.

  4. Effects of NOX-H94 on innate immune response [ Time Frame: 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

  5. Pharmacokinetics: Cmax of NOX-H94 [ Time Frame: Day 1 ]
  6. Pharmacokinetics: AUC of NOX-H94 [ Time Frame: 0-2 weeks ]
  7. Pharmacokinetics: Clearance of NOX-H94 [ Time Frame: 0-2 weeks ]
  8. Pharmacodynamics: effect of NOX-H94 on Red blood cell parameters [ Time Frame: 0- 2 weeks ]
    Change versus baseline and group comparison: reticulocyte hemoglobin content, hemoglobin, mean cell volume, mean cell hemoglobin

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01522794

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Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
TME Pharma AG
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Study Director: Kai Riecke, MD TME Pharma AG
Principal Investigator: Peter Pickkers, MD, PhD Radboud University Medical Center
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: TME Pharma AG
ClinicalTrials.gov Identifier: NCT01522794    
Other Study ID Numbers: SNOXH94C101
2011-005022-22 ( EudraCT Number )
First Posted: February 1, 2012    Key Record Dates
Last Update Posted: November 10, 2014
Last Verified: November 2014
Additional relevant MeSH terms:
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Chronic Disease
Disease Attributes
Pathologic Processes
Systemic Inflammatory Response Syndrome