Effect of BIBT 986 Followed by BIBT 986 Given as IV Infusion on Tissue Factor Triggered Coagulation in Healthy Male Volunteers
Investigation of the Effect of 0.9, 2.25 or 4.5 mg of BIBT 986 Over 1 Hour, Followed by 0.2, 0.5 or 1.0 mg/Hour of BIBT 986 for 7 Hours Given as IV Infusion on Tissue Factor Triggered Coagulation in a Randomised, Placebo Controlled, Dose Escalation Design in Healthy Male Volunteers
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy male subjects as determined by the screening procedure
- Signed written informed consent form in accordance with good clinical practice (GCP) and local legislation was available
- Age ≥ 18 and ≤ 40 years
- Body mass index: BMI ≥ 18 and ≤ 29.9 kg/m2
- Normal findings in medical history and physical examination unless the investigator considered an abnormality to be clinically irrelevant
- Normal laboratory parameters unless the investigator considered an abnormality to be clinically irrelevant
Exclusion Criteria:
- Any finding in the medical examination (including blood pressure, pulse rate, ECG, and laboratory parameters) deviating from normal and of clinical relevance
- History of or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, autoimmune, hormonal disorders, diseases of the central nervous system (such as epilepsy), or psychiatric disorders
- Symptoms of a clinically relevant illness in the 3 weeks before the first trial day
- History of orthostatic hypotension, fainting spells, and blackouts
- Chronic or relevant acute infections
- History of allergy / hypersensitivity (including drug allergy) which was deemed relevant to the trial as judged by the investigator
History of
- any bleeding disorder including prolonged or habitual bleeding
- any familial bleeding disorder
- other haematological disease
- cerebral bleeding (e.g. after a car accident)
- commotio cerebri
- Hereditary deficiency of protein C or S, or a mutation of factor V (Leiden), or any other known abnormality affecting coagulation, fibrinolysis, or platelet function
- Platelet count < 150000/μL
- Any ECG value outside of the reference range of clinical relevance (QRS interval > 110 ms or QTcB (QT interval Bazett correction) > 450 ms will be an obligatory exclusion criterion)
- Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration
- Use of any drugs that might influence the results of the trial within 10 days prior to administration or during the trial
- Participation in another trial with an investigational drug within 2 months prior to administration or during trial
- Participation in an LPS trial within the last six weeks
- Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
- Concurrent or history of drug, alcohol, tobacco or coffee / tea / cola abuse
- Blood donation within 1 month prior to administration or during the trial
- Excessive physical activities within 5 days prior to administration or during the trial
- Seropositivity for hepatitis B surface antigen (HBs-Ag), hepatitis C virus (HCV), HIV 1, or HIV 2 antibodies
- Weight over 95 kg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Experimental: Low dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Experimental: Medium dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Experimental: High dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in activated partial thromboplastin time (aPTT)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in international normalized ratio (INR)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombin time (TT)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in ecarin clotting time (ECT)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in prothrombin fragment (F1+2)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in D-dimer
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombin anti-thrombin complexes (TAT)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in protein C activity
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in antithrombin
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombomodulin
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in tissue factor messenger RNA (mRNA)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in platelet count
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in plasmin antiplasmin complexes (PAP)
Time Frame: Pre-dose, up to day 14 after start of treatment
|
Pre-dose, up to day 14 after start of treatment
|
|
|
Change in soluble P-selectin
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in tumor necrosis factor alpha (TNF alpha)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in interleukin-6 (IL-6)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in primary haemostasis measured by closure times
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Number of subjects with clinically relevant changes in vital signs
Time Frame: up to 14 days after start of treatment
|
blood pressure, pulse rate, body temperature
|
up to 14 days after start of treatment
|
|
Number of subjects with clinically relevant changes in laboratory parameters
Time Frame: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Number of subjects with adverse events
Time Frame: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Number of subjects with clinically relevant changes in ECG
Time Frame: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Change in thrombus precursor protein
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in soluble E-selectin
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Area under the plasma concentration-time curve (AUC)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
Maximum concentration in plasma at the end of the infusion (Cgh)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
Apparent terminal half-life of BIBT 986 in plasma (t1/2)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
Mean residence time of BIBT 986 in the body after intravenous bolus administration (MRT)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
Volume of distribution of BIBT 986 in plasma at steady state (Vss)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
Apparent volume of distribution of BIBT 986 during the terminal phase after intravenous infusion (Vz)
Time Frame: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
Collaborators and Investigators
Sponsor
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Actual)
Primary Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Estimate)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
Other Study ID Numbers
- 1192.11
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