PK/PD of EA-230 During Endotoxemia

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

EA-230 is a newly developed synthetic compound with anti-inflammatory properties. Pre-clinical data indicate that EA-230 may be a valuable treatment for systemic inflammation resulting from a variety of causes such as surgery, trauma, infection, irradiation and others. Although previous studies in healthy volunteers have shown an excellent safety profile, the safety and tolerability of higher doses administered per continuous infusion need to be investigated. Also, the dose-effect relation on systemic inflammation needs to be further elucidated before a phase II trial in patients can be commenced.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Radboud University
• Collaborator: Exponential Biotherapies Inc.

Criteria

Inclusion Criteria:

1. Aged 18 to 35 years inclusive

2. For part 2 only male

3. Subjects and their partners use a reliable way of contraception

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, ECG, and clinical laboratory parameters

Exclusion Criteria:

1. Unwillingness to abstain from any medication, recreational drugs or anti-oxidant vitamin supplements during the course of the study and within 7 days prior to study Day 1.

2. Unwillingness to abstain from nicotine, or alcohol or within 1 day prior to study Day 1

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 study Day 1

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

6. Renal impairment: plasma creatinine >120 µmol/L

7. Liver function tests (alkaline phosphatase, AST, ALT and/or γ-GT) above 2x the upper limit of normal.

8. History of asthma

9. Atopic constitution

10. CRP above 2x the upper limit of normal, or clinically significant acute illness, including infections, within 2 weeks before administration of the study drug.

11. Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration.

12. Known or suspected of not being able to comply with the trial protocol.

13. Known hypersensitivity to any excipients of the drug formulations used.

14. Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.