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

NCT02259881 | Completed Phase 1

• 1 other identifier: 1192.11
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (23)

• Change in activated partial thromboplastin time (aPTT)

  up to 48 hours after start of treatment

• Change in international normalized ratio (INR)

  up to 48 hours after start of treatment

• Change in thrombin time (TT)

  up to 48 hours after start of treatment

• Change in ecarin clotting time (ECT)

  up to 48 hours after start of treatment

• Change in prothrombin fragment (F1+2)

  up to 48 hours after start of treatment

• Change in D-dimer

  up to 48 hours after start of treatment

• Change in thrombin anti-thrombin complexes (TAT)

  up to 48 hours after start of treatment

• Change in protein C activity

  up to 48 hours after start of treatment

• Change in antithrombin

  up to 48 hours after start of treatment

• Change in thrombomodulin

  up to 48 hours after start of treatment

• Change in tissue factor messenger RNA (mRNA)

  up to 48 hours after start of treatment

• Change in platelet count

  up to 48 hours after start of treatment

• Change in plasmin antiplasmin complexes (PAP)

  Pre-dose, up to day 14 after start of treatment

• Change in soluble P-selectin

  up to 48 hours after start of treatment

• Change in tumor necrosis factor alpha (TNF alpha)

  up to 48 hours after start of treatment

• Change in interleukin-6 (IL-6)

  up to 48 hours after start of treatment

• Change in primary haemostasis measured by closure times

  up to 48 hours after start of treatment

• Number of subjects with clinically relevant changes in vital signs

  blood pressure, pulse rate, body temperature

  up to 14 days after start of treatment

• Number of subjects with clinically relevant changes in laboratory parameters

  up to 14 days after start of treatment

• Number of subjects with adverse events

  up to 14 days after start of treatment

• Number of subjects with clinically relevant changes in ECG

  up to 14 days after start of treatment

• Change in thrombus precursor protein

  up to 48 hours after start of treatment

• Change in soluble E-selectin

  up to 48 hours after start of treatment

Secondary Outcomes (6)

• Area under the plasma concentration-time curve (AUC)

  up to 48 hours after start of treatment

• Maximum concentration in plasma at the end of the infusion (Cgh)

  up to 48 hours after start of treatment

• Apparent terminal half-life of BIBT 986 in plasma (t1/2)

  up to 48 hours after start of treatment

• Mean residence time of BIBT 986 in the body after intravenous bolus administration (MRT)

  up to 48 hours after start of treatment

• Volume of distribution of BIBT 986 in plasma at steady state (Vss)

  up to 48 hours after start of treatment

Study Arms (4)

Low dose of BIBT 986 CL

EXPERIMENTAL

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

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

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

Placebo

PLACEBO COMPARATOR

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

Interventions

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

Low dose of BIBT 986 CL

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

Medium dose of BIBT 986 CL

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

High dose of BIBT 986 CL

Placebo DRUG

Placebo

Lipopolysaccharide (LPS), single i.v. bolus DRUG

Endotoxin derived from E. coli bacteria, used for activation of coagulation

High dose of BIBT 986 CL; Low dose of BIBT 986 CL; Medium dose of BIBT 986 CL; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Intake of drugs with a long half-life (\> 24 hours) within 1 month prior to administration

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Lipopolysaccharides

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2014
• First Posted: October 9, 2014
• Study Start: December 1, 2002
• Primary Completion: May 1, 2003
• Last Updated: October 9, 2014

Record last verified: 2014-10