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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NOXXON Pharma AG
ClinicalTrials.gov Identifier:
NCT01522794
First received: January 18, 2012
Last updated: February 15, 2013
Last verified: March 2012
  Purpose

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 Intervention Phase
Anemia of Chronic Disease
Drug: NOX-H94
Drug: Placebo solution
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by NOXXON Pharma AG:

Primary Outcome Measures:
  • serum iron [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
    Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo


Secondary Outcome Measures:
  • Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis [ Time Frame: up to 2 Weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    plasma concentration-time profile T0 to 2 weeks

  • Safety and tolerability [ Time Frame: up to 2 Weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: AUC of NOX-H94 [ Time Frame: 0-2 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Clearance of NOX-H94 [ Time Frame: 0-2 weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamics: effect of NOX-H94 on Red blood cell parameters [ Time Frame: 0- 2 weeks ] [ Designated as safety issue: No ]
    Change versus baseline and group comparison: reticulocyte hemoglobin content, hemoglobin, mean cell volume, mean cell hemoglobin


Enrollment: 24
Study Start Date: January 2012
Study Completion Date: April 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NOX-H94
Single dose of NOX-H94
Drug: NOX-H94
single i.v. infusion
Placebo Comparator: Placebo
Single dose of placebo control
Drug: Placebo solution
single i.v. infusion

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01522794

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
NOXXON Pharma AG
Investigators
Study Director: Kai Riecke, MD NOXXON Pharma AG
Principal Investigator: Peter Pickkers, MD, PhD Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: NOXXON Pharma AG
ClinicalTrials.gov Identifier: NCT01522794     History of Changes
Other Study ID Numbers: SNOXH94C101, 2011-005022-22
Study First Received: January 18, 2012
Last Updated: February 15, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Anemia
Chronic Disease
Endotoxemia
Hematologic Diseases
Disease Attributes
Pathologic Processes
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Inflammation

ClinicalTrials.gov processed this record on April 17, 2014