Clinical trial NCT02211170: Effect of Single Oral Dose BIRB 796 BS on Endotoxin-induced Inflammatory Responses in Healthy Human Subjects
Official title: The Effect of Single Oral Dose BIRB 796 BS (50 and 600 mg) on Endotoxin-induced Inflammatory Responses in Healthy Human Subjects. A Placebo-controlled, Randomised, Parallel, Double-blinded Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-07
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to determine the effect of a single dose BIRB 796 BS on systemic inflammatory responses induced by endotoxin in healthy humans


Eligibility criteria: 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

Primary outcomes:
measure: Reduction of tumour necrosis factor alpha (TNFα) concentration
timeFrame: up to 2 days
Secondary outcomes:
measure: Reduction of pro-inflammatory cytokines (IL-6, IL-8, G-CSF)
timeFrame: up to 2 days
measure: Reduction of anti-inflammatory cytokine and cytokine inhibitors (IL-10, IL-12p40, soluble TNF receptor (sTNFr) type 1, IL-1ra)
timeFrame: up to 2 days
measure: Reduction of Acute Phase Proteins (C-reactive protein, Haptoglobin)
timeFrame: up to 2 days
measure: Reduction of Endothelial Activation Markers (von Willebrand Factor, soluble E-selectin)
timeFrame: up to 2 days
measure: Reduction of Granulocyte Responses (white blood cell (WBC) count with differential, elastase, elastase-á1-antitrypsin complexes)
timeFrame: up to 2 days
measure: Reduction of flow Cytometry Cell Surface Markers (Mac-1 (macrophage-1 antigen), L-Selectin)
timeFrame: up to 2 days
measure: Reduction of ex vivo p38 mitogen-activated protein kinase (MAPK) phosphorylation activity
timeFrame: up to 2 days
measure: Occurence and severity of with chills, nausea, vomiting, abdominal pain, backache, headache, myalgia, fever
timeFrame: up to 2 days
measure: Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure, temperature)
timeFrame: up to 14 days
measure: Number of patients with abnormal changes in laboratory parameters
timeFrame: up to 14 days
measure: Number of patients with adverse events
timeFrame: up to 14 days
measure: Assessment of Global Clinical Tolerability on a 4-point scale
timeFrame: after 14 days
measure: Maximum plasma concentration (Cmax)
timeFrame: up to 27 hours after drug administration
measure: Time at which Cmax occurred (tmax)
timeFrame: up to 27 hours after drug administration
measure: Elimination half life (t1/2),
timeFrame: up to 27 hours after drug administration
measure: Area under the plasma concentration-time curve for different time points(AUC)
timeFrame: up to 27 hours after drug administration
measure: Apparent clearance (CL/F)
timeFrame: up to 27 hours after drug administration
measure: Elimination rate constant (λz)
timeFrame: up to 27 hours after drug administration
measure: Mean residence time (MRT)
timeFrame: up to 27 hours after drug administration
measure: Apparent volume of distribution (Vz/F)
timeFrame: up to 27 hours after drug administration
Other outcomes:
Locations:
Study officials:
References: