Effect of Single Oral Dose BIRB 796 BS on Endotoxin-induced Inflammatory Responses in Healthy Human Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: BIBR 796 BS, low dose; Drug: Placebo; Drug: BIBR 796 BS, high dose; Drug: Lipopolysaccharide

• Registration Number: NCT02211170
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2000-02
• Primary Completion: 2000-04
• Status Verified: 2014-08
• Study First Submitted: 2014-08-05
• Study First Submitted QC: 2014-08-05
• Last Update Submitted: 2014-08-05
• Study First Posted: 2014-08-07
• Last Update Posted: 2014-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIBR 796 BS, high dose	Lipopolysaccharide	-
Placebo	Lipopolysaccharide	-
BIBR 796 BS, low dose	Lipopolysaccharide	-
BIBR 796 BS, low dose	BIBR 796 BS, low dose	-
Placebo	Placebo	-
BIBR 796 BS, high dose	BIBR 796 BS, high dose	-

Primary Outcome Measures

Name	Time	Method
Reduction of tumour necrosis factor alpha (TNFα) concentration	up to 2 days

Secondary Outcome Measures

Name	Time	Method
Apparent clearance (CL/F)	up to 27 hours after drug administration
Number of patients with adverse events	up to 14 days
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 ex vivo p38 mitogen-activated protein kinase (MAPK) phosphorylation activity	up to 2 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
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
Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure, temperature)	up to 14 days
Reduction of flow Cytometry Cell Surface Markers (Mac-1 (macrophage-1 antigen), L-Selectin)	up to 2 days
Occurence and severity of with chills, nausea, vomiting, abdominal pain, backache, headache, myalgia, fever	up to 2 days
Maximum plasma concentration (Cmax)	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
Assessment of Global Clinical Tolerability on a 4-point scale	after 14 days
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
Mean residence time (MRT)	up to 27 hours after drug administration
Apparent volume of distribution (Vz/F)	up to 27 hours after drug administration
Elimination rate constant (λz)	up to 27 hours after drug administration