Effect of BIBT 986 Followed by BIBT 986 Given as IV Infusion on Tissue Factor Triggered Coagulation in Healthy Male Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Low dose of BIBT 986 CL, per i.v. infusion; Drug: High dose of BIBT 986 CL, per i.v. infusion; Drug: Placebo; Drug: Lipopolysaccharide (LPS), single i.v. bolus; Drug: Medium dose of BIBT 986 CL, per i.v. infusion

Study type: Interventional

Funder types: Industry

Identifiers

NCT02259881

1192.11

Details and patient eligibility

About

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

Enrollment: 64 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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64 participants in 4 patient groups, including a placebo group

Low dose of BIBT 986 CL

Experimental group

Treatment:

Drug: Low dose of BIBT 986 CL, per i.v. infusion

Drug: Lipopolysaccharide (LPS), single i.v. bolus

Medium dose of BIBT 986 CL

Experimental group

Treatment:

Drug: Medium dose of BIBT 986 CL, per i.v. infusion

Drug: Lipopolysaccharide (LPS), single i.v. bolus

High dose of BIBT 986 CL

Experimental group

Treatment:

Drug: Lipopolysaccharide (LPS), single i.v. bolus

Drug: High dose of BIBT 986 CL, per i.v. infusion

Placebo

Placebo Comparator group

Treatment:

Drug: Lipopolysaccharide (LPS), single i.v. bolus

Drug: Placebo