Pharmacokinetics and Pharmacodynamics of BIWH 3 in Healthy Duffy Positive vs. Duffy Negative Male Volunteers

Study Overview
=================
Brief Summary
-----------------
Study to compare the pharmacokinetic and pharmacodynamic effects of escalating dosages of recombinant human pyro-Glu MCP-1 (BIWH 3) in Duffy positive vs. Duffy negative healthy male volunteers: plasma levels of monocyte chemotactic protein-1 (MCP-1) and markers of leukocyte, coagulation, platelet and endothelial activation will be quantified; To examine the safety of BIWH 3 in this setting

Official Title
-----------------
Pharmacokinetics and Pharmacodynamics of BIWH 3: a Randomised, Placebo-controlled, Double Blind Dose Escalation Study (0.02, 0.06, 0.2, 0.6, and 2.0 μg/kg Intravenous Over One Hour) in Healthy Duffy Positive vs. Duffy Negative Male Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BIWH 3
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male subjects as determined by results of screening Erythrocyte Fy positive and negative individuals because expression of the Duffy (Fy) receptor may influence MCP-1 plasma levels in humans Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Age ≥ 18 and ≤ 50 years Body mass index: ≥18 kg/m2 and < 30 kg/m2 Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Normal laboratory variables unless the investigator considers an abnormality to be clinically irrelevant Normal pharmacodynamic variables as determined at baseline visit Normal response to glucose tolerance test Exclusion Criteria: Any finding in the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Current or history of: gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, autoimmune, hormonal disorders, diseases of the central nervous system (such as epilepsy), psychiatric disorders or cancer Symptoms of a clinically relevant illness in the 3 weeks prior to planned administration of study drug History of orthostatic hypotension, fainting spells and blackouts Chronic or relevant acute infections History of allergy / hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Any Electrocardiogram (ECG) value outside the reference range of clinical relevance including, but not limited to QRS interval > 110 ms or QTcB > 450 ms Intake of drugs with a long half-life (> 24 hours) within 1 month prior to planned administration of study drug Use of any drugs which might influence the results of the trial within 10 days prior to planned administration or during the trial Participation in another trial with an investigational drug within 2 months prior to planned administration or during trial Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days Current or history of drug, alcohol, tobacco or caffeine abuse Blood donation within 1 month prior to planned administration or during the trial Excessive physical activities within 5 days prior to planned administration of study drug or during the trial Seropositivity for hepatitis B antigen (HBs-Ag), hepatitis C (HCV), HIV 1, or HIV 2 antibodies Weight over 95 kg

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIWH 3<br>single escalating dose | Drug: BIWH 3<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) |  | up to 14 days after drug administration | 
| Area under the plasma concentration-time curve up to the last quantifiable plasma concentration (AUC0-tz) |  | up to 14 days after drug administration | 
| maximum BIWH 3 plasma concentration (Cmax) |  | up to 14 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monocyte activation | Quantification of leukocyte surface markers by flow cytometry | up to 14 days after drug administration | 
| Platelet cell activation | Quantification of soluble P-selectin by enzyme immunoassay | up to 14 days after drug administration | 
| Endothelial cell activation | Quantification of soluble E-selectin by enzyme immunoassay | up to 14 days after drug administration | 
| Inflammatory response | Quantification of mRNA expression of IL-1 by reverse transcriptase-polymerase chain reaction (RT-PCR) | up to 14 days after drug administration | 
| Activation of coagulation | Prothrombin fragment levels via an enzyme-immunoassay | up to 14 days after drug administration | 
| Number of subjects with adverse events |  | up to 14 days after drug administration | 
| Number of subjects with clinically significant findings in vital signs | blood pressure, pulse rate, body temperature | up to 14 days after drug administration | 
| Number of subjects with clinically significant findings in ECG |  | up to 14 days after drug administration | 
| Number of subjects with clinically significant findings in laboratory tests |  | up to 14 days after drug administration |