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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

Tracking Information
First Submitted Date  ICMJE January 18, 2012
First Posted Date  ICMJE February 1, 2012
Last Update Posted Date November 10, 2014
Study Start Date  ICMJE January 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2012)
serum iron [ Time Frame: 9 hours ]
Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2012)
  • 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
  • Pharmacokinetic profile of NOX-H94 [ Time Frame: 12 time points over 2 Weeks ]
    plasma concentration-time profile T0 to 2 weeks
  • 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.
  • 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
  • Pharmacokinetics: Cmax of NOX-H94 [ Time Frame: Day 1 ]
  • Pharmacokinetics: AUC of NOX-H94 [ Time Frame: 0-2 weeks ]
  • Pharmacokinetics: Clearance of NOX-H94 [ Time Frame: 0-2 weeks ]
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Anemia of Chronic Disease
Intervention  ICMJE
  • Drug: NOX-H94
    single i.v. infusion
    Other Name: lexaptepid pegol
  • Drug: Placebo solution
    single i.v. infusion
Study Arms  ICMJE
  • Experimental: NOX-H94
    Single dose of NOX-H94
    Intervention: Drug: NOX-H94
  • Placebo Comparator: Placebo
    Single dose of placebo control
    Intervention: Drug: Placebo solution
Publications * van Eijk LT, John AS, Schwoebel F, Summo L, Vauléon S, Zöllner 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 27, 2012)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01522794
Other Study ID Numbers  ICMJE SNOXH94C101
2011-005022-22 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party TME Pharma AG
Original Responsible Party Same as current
Current Study Sponsor  ICMJE TME Pharma AG
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kai Riecke, MD TME Pharma AG
Principal Investigator: Peter Pickkers, MD, PhD Radboud University Medical Center
PRS Account TME Pharma AG
Verification Date November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP