Healthy
Conditions
Brief summary
Study to assess safety, pharmacokinetics and pharmacodynamics of BIRB 796 BS in escalating multiple doses with and without a 64 g fat breakfast at the 50 mg dose level
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 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 ≤ 45 years * Broca ≥ - 20% and ≤ + 20%
Exclusion criteria
* Any findings of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders * Surgery of gastrointestinal tract (except appendectomy) * History of orthostatic hypotension, fainting spells and blackouts * Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders * Chronic or relevant acute infections * 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) within 1 month prior to administration or during the trial) * Use of any drugs which might influence the results of the trial within 10 days prior to administration or during trial * Participation in another trial with an investigational drug within 2 months prior to administration or during trial * Smoker (\> 10 cigarettes or 3 cigars or 3 pipes/day) * Inability to refrain from smoking on study days * Alcohol abuse (\> 60 g/day) * Drug abuse * Blood donation \> 400 ml within 1 month prior to administration or during the trial * Excessive physical activities within 5 days prior to administration or during the trial * Any laboratory value outside the reference range of clinical relevance including, but not limited to total white cell count ≥ 10 x 10\*\*9/L, C-reactive protein ≥ 4.5 mg/L, Gamma-Glutamyl Transferase ≥ 40 U/L, any hemoglobin or \> 15 mg/dl protein or urine dipstick, abnormal Multitest® assessment of cellular immunity * History of any familial bleeding disorder * Inability to comply with dietary regimen of study centre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients with clinically relevant changes in laboratory parameters | up to day 16 |
| Number of patients with abnormal findings in electrocardiogram (ECG) | up to day 16 |
| Number of patients with adverse events | up to 30 days |
| Assessment of tolerability on a 4-point scale | day 16 |
| Number of patients with clinically relevant changes in vital signs | up to 16 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean residence time (MRT) | up to day 9 | — |
| Apparent clearance (CL/f) | up to day 9 | — |
| Apparent volume of distribution (Vz/F) | up to day 9 | — |
| Maximum plasma concentration (Cmax) for several time points | up to day 9 | — |
| Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with tumour necrosis factor (TNF) α | up to day 9 | Change in the Mac-1 / L-selectin ratio |
| Assessment of TNFα production by ex vivo stimulation of whole blood with endotoxin | up to day 9 | — |
| Changes in cellular immune response measured by Multitest® | Day 8 | — |
| Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with formyl-methionyl-leucyl-phenylalanine (fMLP) | up to day 9 | Change in the Mac-1 / L-selectin ratio |
| Area under the plasma concentration-time curve (AUC) for several time points | up to day 9 | — |
| Time to maximum concentration (tmax) | up to day 9 | — |
| Elimination rate constant (λz) | up to day 9 | — |
| Terminal half-life (t1/2) | up to day 9 | — |
Outcome results
None listed