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
- Conditions
- Anemia of Chronic disease10002252inflammation associated anemia1000208610003816
- Registration Number
- NL-OMON35593
- Lead Sponsor
- OXXON Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
1. Written informed consent to participate in this trial
2. Male subjects aged 18 to 35 years inclusive
3. Subjects and their female partners have to agree to use a reliable way of contraception from screening until 2 months after study drug administration.
4. BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg
5. Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters
6. Serum iron and red blood parameters Hb, MCV, ferritin, serum iron, and total iron binding capacity within reference range
1. Use of any medication, recreational drugs or anti-oxidant vitamin supplements within 7 days prior to profiling day
2. Use of caffeine, nicotine, or alcohol or within 1 day prior to profiling day
3. Previous participation in a trial where LPS was administered
4. Surgery or trauma with significant blood loss or blood donation within 3 months prior to profiling day
5. History, signs or symptoms of cardiovascular disease, in particular
• History of frequent vaso-vagal collapse or of orthostatic hypotension
• Resting pulse rate <=45 or >=100 beats / min
• Hypertension (RR systolic >160 or RR diastolic >90)
• Hypotension (RR systolic <100 or RR diastolic <50)
• conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
6. Renal impairment: plasma creatinine >120 µmol/L
7. Liver function tests (alkaline phosphatase, AST, ALT and γ-GT) outside of the reference range or total bilirubin >20 µmol/L
8. Hemoglobin or iron parameters (iron, transferrin saturation, ferritin) outside of the reference ranges
9. History of asthma
10. Immuno-deficiency
11. Positive test of HIV type 1/2 antibodies, HBs antigen, HBc antibodies and HCV antibodies unless antibody titer is induced by vaccination
12. CRP > reference range or clinically significant acute illness, including infections, within 2 weeks before profiling day of study drug.
13. Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration
14. Known or suspected of not being able to comply with the trial protocol.
15. Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint<br /><br><br /><br>• Change in serum iron concentration at 9 hours after LPS administration versus<br /><br>baseline; comparison of subjects treated with NOX H94 versus placebo. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints<br /><br>• Change in serum iron concentrations at 6 and 12 hours after LPS<br /><br>administration versus baseline<br /><br>• Concentrations of serum iron and of markers of iron homeostasis up to 48 h<br /><br>after LPS injection: serum iron, transferrin saturation (TSAT), ferritin,<br /><br>reticulocyte hemoglobin content (CHR), hemoglobin (Hb), mean cell volume (MCV),<br /><br>mean cell hemoglobin (MCH): AUC of serum iron concentrations, ANOVA of repeat<br /><br>measures of all data points<br /><br>• Concentration of hepcidin up to 1 week after LPS injection<br /><br>• Concentrations of pro-inflammatory and anti-inflammatory cytokines up to 48 h<br /><br>after LPS injection: TNF a, IL 6, IL 1RA, IL 10 to document the inflammatory<br /><br>reaction<br /><br>• Pharmacokinetic profile of NOX H94<br /><br>• Safety and tolerability</p><br>