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: June 25, 2014
Last verified: June 2014
  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
Other Name: lexaptepid pegol
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: June 25, 2014
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 August 27, 2014