Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model
This study has been completed.
Sponsor:
Noxxon Pharma AG
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
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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 May 21, 2013