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History of Changes for Study: NCT01522794
Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model
Latest version (submitted November 7, 2014) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 27, 2012 None (earliest Version on record)
2 March 22, 2012 Recruitment Status, Study Status and Contacts/Locations
3 March 26, 2012 Study Status and Study Design
4 April 18, 2012 Recruitment Status and Study Status
5 September 25, 2012 Study Design and Study Status
6 February 15, 2013 References and Study Status
7 June 25, 2014 Study Status and Arms and Interventions
8 November 7, 2014 Study Status and References
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Study NCT01522794
Submitted Date:  January 27, 2012 (v1)

Open or close this module Study Identification
Unique Protocol ID: SNOXH94C101
Brief Title: Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model
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
Secondary IDs: 2011-005022-22 [EudraCT Number]
Open or close this module Study Status
Record Verification: January 2012
Overall Status: Recruiting
Study Start: January 2012
Primary Completion: March 2012 [Anticipated]
Study Completion: March 2012 [Anticipated]
First Submitted: January 18, 2012
First Submitted that
Met QC Criteria:
January 27, 2012
First Posted: February 1, 2012 [Estimate]
Last Update Submitted that
Met QC Criteria:
January 27, 2012
Last Update Posted: February 1, 2012 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: TME Pharma AG
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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:
Open or close this module Conditions
Conditions: Anemia of Chronic Disease
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 24 [Anticipated]
Open or close this module Arms and Interventions
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
Open or close this module Outcome Measures
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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 35 Years
Sex: Male
Gender Based:
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
Open or close this module Contacts/Locations
Study Officials: Kai Riecke, MD
Study Director
TME Pharma AG
Peter Pickkers, MD, PhD
Principal Investigator
Radboud University Medical Center
Locations: Netherlands
Radboud University Nijmegen Medical Centre
[Recruiting]
Nijmegen, Netherlands, 6500 HB
Contact:Contact: Lucas vanEijk, MD +31-24-3611111 Ext. 81 2215
Contact:Principal Investigator: Peter Pickkers, MD PhD
Contact:Sub-Investigator: Lucas vanEijk, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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