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
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 1
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Komparátor placeba: Placebo
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Experimentální: Low dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Experimentální: Medium dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
|
Experimentální: High dose of BIBT 986 CL
|
Endotoxin derived from E. coli bacteria, used for activation of coagulation
|
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Change in activated partial thromboplastin time (aPTT)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in international normalized ratio (INR)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombin time (TT)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in ecarin clotting time (ECT)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in prothrombin fragment (F1+2)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in D-dimer
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombin anti-thrombin complexes (TAT)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in protein C activity
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in antithrombin
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in thrombomodulin
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in tissue factor messenger RNA (mRNA)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in platelet count
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in plasmin antiplasmin complexes (PAP)
Časové okno: 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
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in tumor necrosis factor alpha (TNF alpha)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in interleukin-6 (IL-6)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in primary haemostasis measured by closure times
Časové okno: 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
Časové okno: 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
Časové okno: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Number of subjects with adverse events
Časové okno: 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
Časové okno: up to 14 days after start of treatment
|
up to 14 days after start of treatment
|
|
|
Change in thrombus precursor protein
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
|
|
Change in soluble E-selectin
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
|
Area under the plasma concentration-time curve (AUC)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: up to 48 hours after start of treatment
|
up to 48 hours after start of treatment
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další identifikační čísla studie
Další identifikační čísla studie
- 1192.11
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