Clinical trial NCT02259881: Effect of BIBT 986 Followed by BIBT 986 Given as IV Infusion on Tissue Factor Triggered Coagulation in Healthy Male Volunteers
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-09
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare with placebo the anticoagulant activity of three dosages of BIBT 986 on parameters of coagulation, platelet activation and inflammation in a model of tissue factor triggered activation of the coagulation system; to examine the safety of BIBT 986 in this setting


Eligibility criteria: 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

Primary outcomes:
measure: Change in activated partial thromboplastin time (aPTT)
timeFrame: up to 48 hours after start of treatment
measure: Change in international normalized ratio (INR)
timeFrame: up to 48 hours after start of treatment
measure: Change in thrombin time (TT)
timeFrame: up to 48 hours after start of treatment
measure: Change in ecarin clotting time (ECT)
timeFrame: up to 48 hours after start of treatment
measure: Change in prothrombin fragment (F1+2)
timeFrame: up to 48 hours after start of treatment
measure: Change in D-dimer
timeFrame: up to 48 hours after start of treatment
measure: Change in thrombin anti-thrombin complexes (TAT)
timeFrame: up to 48 hours after start of treatment
measure: Change in protein C activity
timeFrame: up to 48 hours after start of treatment
measure: Change in antithrombin
timeFrame: up to 48 hours after start of treatment
measure: Change in thrombomodulin
timeFrame: up to 48 hours after start of treatment
measure: Change in tissue factor messenger RNA (mRNA)
timeFrame: up to 48 hours after start of treatment
measure: Change in platelet count
timeFrame: up to 48 hours after start of treatment
measure: Change in plasmin antiplasmin complexes (PAP)
timeFrame: Pre-dose, up to day 14 after start of treatment
measure: Change in soluble P-selectin
timeFrame: up to 48 hours after start of treatment
measure: Change in tumor necrosis factor alpha (TNF alpha)
timeFrame: up to 48 hours after start of treatment
measure: Change in interleukin-6 (IL-6)
timeFrame: up to 48 hours after start of treatment
measure: Change in primary haemostasis measured by closure times
timeFrame: up to 48 hours after start of treatment
measure: Number of subjects with clinically relevant changes in vital signs
timeFrame: up to 14 days after start of treatment
measure: Number of subjects with clinically relevant changes in laboratory parameters
timeFrame: up to 14 days after start of treatment
measure: Number of subjects with adverse events
timeFrame: up to 14 days after start of treatment
measure: Number of subjects with clinically relevant changes in ECG
timeFrame: up to 14 days after start of treatment
measure: Change in thrombus precursor protein
timeFrame: up to 48 hours after start of treatment
measure: Change in soluble E-selectin
timeFrame: up to 48 hours after start of treatment
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: up to 48 hours after start of treatment
measure: Maximum concentration in plasma at the end of the infusion (Cgh)
timeFrame: up to 48 hours after start of treatment
measure: Apparent terminal half-life of BIBT 986 in plasma (t1/2)
timeFrame: up to 48 hours after start of treatment
measure: Mean residence time of BIBT 986 in the body after intravenous bolus administration (MRT)
timeFrame: up to 48 hours after start of treatment
measure: Volume of distribution of BIBT 986 in plasma at steady state (Vss)
timeFrame: up to 48 hours after start of treatment
measure: Apparent volume of distribution of BIBT 986 during the terminal phase after intravenous infusion (Vz)
timeFrame: up to 48 hours after start of treatment
Other outcomes:
Locations:
Study officials:
References: