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
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 1
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Placebo komparator: Placebo
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Eksperimentel: Low dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Eksperimentel: Medium dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Eksperimentel: High dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in activated partial thromboplastin time (aPTT)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in international normalized ratio (INR)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombin time (TT)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in ecarin clotting time (ECT)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in prothrombin fragment (F1+2)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in D-dimer
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombin anti-thrombin complexes (TAT)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in protein C activity
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in antithrombin
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombomodulin
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in tissue factor messenger RNA (mRNA)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in platelet count
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in plasmin antiplasmin complexes (PAP)
Tidsramme: 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
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in tumor necrosis factor alpha (TNF alpha)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in interleukin-6 (IL-6)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in primary haemostasis measured by closure times
Tidsramme: 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
Tidsramme: 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
Tidsramme: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Number of subjects with adverse events
Tidsramme: 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
Tidsramme: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Change in thrombus precursor protein
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in soluble E-selectin
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Area under the plasma concentration-time curve (AUC)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- 1192.11
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