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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BIBR 796 BS, low dose; Drug: Lipopolysaccharide; Drug: BIBR 796 BS, high dose

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Drug: Lipopolysaccharide; Lipopolysaccharide (LPS) for endotoxin challenge
Experimental: BIBR 796 BS, low dose	Drug: BIBR 796 BS, low dose; Drug: Lipopolysaccharide; Lipopolysaccharide (LPS) for endotoxin challenge
Experimental: BIBR 796 BS, high dose	Drug: Lipopolysaccharide; Lipopolysaccharide (LPS) for endotoxin challenge; Drug: BIBR 796 BS, high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction of tumour necrosis factor alpha (TNFα) concentration	up to 2 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Reduction of pro-inflammatory cytokines (IL-6, IL-8, G-CSF)	up to 2 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 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
Number of patients with adverse events	up to 14 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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2000
• Primary Completion (Actual): April 1, 2000

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 7, 2014

Study Record Updates

• Last Update Posted (Estimate): August 7, 2014
• Last Update Submitted That Met QC Criteria: August 5, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1175.4