A randomized double-blind placebo-controlled phase 1 study regarding safety, tolerability and pharmacokinetics/-dynamics of escalating single intravenous doses of ADRECIZUMAB (HAM 8101) in healthy male subjects.
- Conditions
- Sepsissevere bacterial infection.10004018
- Registration Number
- NL-OMON43493
- Lead Sponsor
- Adrenomed 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 prior to any study mandated
procedure.
2. Male subjects aged 18 to 35 years, inclusive.
3. Subjects have to agree to use a reliable way of contraception with
their partners 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 and a upper limit of 100 kg.
5. Healthy as determined by medical history, physical examination, vital
signs, 12 lead electrocardiogram, and clinical laboratory parameters
1. Unwillingness to abstain from any medication, recreational drugs, anti-oxidant or vitamin supplements during the course of the study and within 7 days prior to the treatment day.
2. Unwillingness to abstain from smoking or alcohol 1 day prior to the treatment day and during the first 24 hours of the study.
3. Surgery or trauma with significant blood loss or blood donation within 3 months prior to the treatment day.
4. History, signs or symptoms of cardiovascular disease, in particular:
* History of frequent vasovagal 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
* Any chronic cardiac arrhythmias, except PAC*s, PVC*s
5. Renal impairment: plasma creatinine >120 µmol/L
6. Liver function tests (alkaline phosphatase, AST, ALT and/or *-GT) above 2x the upper limit of normal.
7. History of asthma
8. Atopic constitution
9. CRP above 2x the upper limit of normal or clinically significant acute illness, including infections, within 2 weeks before administration of the study drug.
10. Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration.
11. Known or suspected of not being able to comply with the trial protocol.
12. Known hypersensitivity to any excipients of the drug formulations used.
13. 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>Adverse events<br /><br>Vital signs during the first 8 hours after administration of ADRECIZUMAB:<br /><br>- Heart rate (continuously by ECG leads)<br /><br>- Blood pressure (continuously by intra-arterial line)<br /><br>- Oxygen saturation (continuously by pulse-oximetry)<br /><br>- Temperature (measured intermittently in the ear by infrared thermometer)<br /><br>Local tolerability at site of i.v. infusion<br /><br>Safety laboratory parameters:<br /><br>- Hb, Ht, leucocytes, thrombocytes, leucocyte differential blood count,<br /><br>sodium, potassium, creatinine, urea, alkaline phosphatase, ALT, AST, *GT, CK,<br /><br>PCT, CRP.<br /><br>-12-lead electrocardiogram (ECG), at baseline, within 1 hour after<br /><br>ADRECIZUMAB administration, and at 7 to 8 hrs after ADRECIZUMAB administration.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Pharmacokinetics of ADRECIZUMAB: AUC, Cmax, terminal t1/2, Cl, V.<br /><br>* Blood plasma levels of adrenomedullin<br /><br>* Ex vivo cytokine production (whole blood will be stimulated with LPS after<br /><br>which cytokine production will be determined by ELISA).</p><br>