Healthy
Conditions
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
Interventions
DRUGBIWH 3
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory response | up to 14 days after drug administration | Quantification of mRNA expression of IL-1 by reverse transcriptase-polymerase chain reaction (RT-PCR) |
| Activation of coagulation | up to 14 days after drug administration | Prothrombin fragment levels via an enzyme-immunoassay |
| Number of subjects with adverse events | up to 14 days after drug administration | — |
| Monocyte activation | up to 14 days after drug administration | Quantification of leukocyte surface markers by flow cytometry |
| 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 | — |
| Number of subjects with clinically significant findings in vital signs | up to 14 days after drug administration | blood pressure, pulse rate, body temperature |
| Platelet cell activation | up to 14 days after drug administration | Quantification of soluble P-selectin by enzyme immunoassay |
| Endothelial cell activation | up to 14 days after drug administration | Quantification of soluble E-selectin by enzyme immunoassay |
Outcome results
None listed