Randomized double blind placebo-controlled clinical safety, tolerability and pharmacokinetic/-dynamic study on the effects of escalating single intravenous doses of EA-230 on the innate immune response during experimental human endotoxemia

Completed

Conditions: inflammatory response
10027665
10038430

Registration Number: NL-OMON40791

Lead Sponsor: Exponential Biotherapies inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 60

Inclusion Criteria

1.Written informed consent to participate in this trial prior to any study-mandated procedure.
2.Subjects aged 18 to 35 years inclusive, for part 2 only male subjects will be included.
3.Subjects and their partners have to agree to use a reliable way of contraception from study entry until 3 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.Negative results for hard drug use from urine drug screen at screening

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 studyDay 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 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/or γ-GT) above 2x the upper limit of normal

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part 1: Safety and tolerability of EA-230<br /><br><br /><br>Part 2: Modulation by EA-230 of the LPS-induced inflammatory response,<br /><br>quantified by the change in area under the curve (AUC) of the concentration *<br /><br>time curve of TNF-a during endotoxemia</p><br>

Secondary Outcome Measures