Healthy
Conditions
Brief summary
Study to determine the effect of a single dose BIRB 796 BS on systemic inflammatory responses induced by endotoxin in healthy humans
Interventions
DRUGBIBR 796 BS, low dose
DRUGBIBR 796 BS, high dose
DRUGPlacebo
Lipopolysaccharide (LPS) for endotoxin challenge
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects as determined by results of screening * Signed written informed consent in accordance with Good Clinical Practice and local legislation * Age ≥18 and ≤ 35 years * Broca ≥- 20 % and ≤ + 20% * Able to communicate well with the investigator and to comply with study requirements
Exclusion criteria
* Any finding of the medical examination (including blood pressure, pulse rate and EKG) deviating from normal and of clinical relevance * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Surgery of gastrointestinal tract (except appendectomy) * Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders * History of orthostatic hypotension, fainting spells or blackouts * Chronic or relevant acute infections within 14 days of enrolment * History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator * Intake of drugs with a long half-life (\> 24 hours) (\< 1 month prior to administration or during the trial) * Use of any drugs, which might influence the results of the trial (\< 10 days prior to administration or during the trial) * Participation in another trial with an investigational drug (\< 3 months prior to administration or during trial) * Smoker (\> 10 cigarettes or \>3 cigars or \>3 pipes/day) * Inability to refrain from smoking on trial days * Alcohol abuse (\> 60 g/day) * Drug abuse * Blood donation or loss \> 400 ml (\< 2 month prior to administration or during the trial) * Excessive physical activities (\< 24 hours prior to administration or during the trial) * Any laboratory value outside the reference range of clinical relevance * History of any familial bleeding disorder * Weight \> 150 kg * Prior confirmed or suspected receipt of a monoclonal antibody
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction of tumour necrosis factor alpha (TNFα) concentration | up to 2 days |
Secondary
| Measure | Time frame |
|---|---|
| Reduction of anti-inflammatory cytokine and cytokine inhibitors (IL-10, IL-12p40, soluble TNF receptor (sTNFr) type 1, IL-1ra) | up to 2 days |
| Reduction of Acute Phase Proteins (C-reactive protein, Haptoglobin) | up to 2 days |
| Reduction of Endothelial Activation Markers (von Willebrand Factor, soluble E-selectin) | up to 2 days |
| Reduction of Granulocyte Responses (white blood cell (WBC) count with differential, elastase, elastase-á1-antitrypsin complexes) | up to 2 days |
| Reduction of flow Cytometry Cell Surface Markers (Mac-1 (macrophage-1 antigen), L-Selectin) | up to 2 days |
| Reduction of ex vivo p38 mitogen-activated protein kinase (MAPK) phosphorylation activity | up to 2 days |
| Occurence and severity of with chills, nausea, vomiting, abdominal pain, backache, headache, myalgia, fever | up to 2 days |
| Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure, temperature) | up to 14 days |
| Number of patients with abnormal changes in laboratory parameters | up to 14 days |
| Reduction of pro-inflammatory cytokines (IL-6, IL-8, G-CSF) | up to 2 days |
| Assessment of Global Clinical Tolerability on a 4-point scale | after 14 days |
| Maximum plasma concentration (Cmax) | up to 27 hours after drug administration |
| Time at which Cmax occurred (tmax) | up to 27 hours after drug administration |
| Elimination half life (t1/2), | up to 27 hours after drug administration |
| Area under the plasma concentration-time curve for different time points(AUC) | up to 27 hours after drug administration |
| Apparent clearance (CL/F) | up to 27 hours after drug administration |
| Elimination rate constant (λz) | up to 27 hours after drug administration |
| Mean residence time (MRT) | up to 27 hours after drug administration |
| Apparent volume of distribution (Vz/F) | up to 27 hours after drug administration |
| Number of patients with adverse events | up to 14 days |
Outcome results
None listed