LPS induced acute inflammatory state in healthy volunteers
Conditions
Interventions
Trade Name: Zontivity
Product Name: Vorapaxar
Pharmaceutical Form: Tablet
INN or Proposed INN: Vorapaxar
CAS Number: 618385-01-6
Current Sponsor code: Vorapaxar
Other descriptive name: VORAPAXAR
Conce
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • =18 years of age • =60 kg bodyweight • Normal findings in medical history and physical examination unless the investigator considers the abnormality to be clinically irrelevant • Normal laboratory values unless the investigator considers abnormalities to be clinically irrelevant • Willingness to comply with the trial’s safety demands (to refrain from excessive sporting activities two weeks after Vorapaxar intake, i.e. full contact sports, climbing, mountain biking etc.) • Ability to understand the purpose and nature of the study, as well as the associated risks • No planned surgeries or other medical interventions in the planned study period Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Intake of any drugs that may interfere with the trial’s endpoints or drugs (i.e. platelet inhibitors, anticoagulants, CYP3A4 inhibitors, NSAIDs, SSRI, SNRI) • Positive results of HIV or hepatitis virology • Acute illness with systemic inflammatory reactions • Known allergies, hypersensitivities or intolerances to any of the used substances • Acute or recent bleeding episodes, increased risk of bleeding at the discretion of the investigator • History of stroke, transient ischemic attacks or intracerebral hemorrhage • Known coagulation or platelet disorders • Participation in an LPS trial within 6 weeks of the first study day • Severe liver or kidney dysfunction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether vorapaxar reduces LPS induced coagulation activation assessed by prothrombin fragments F1+2;Secondary Objective: to investigate whether vorapaxar reduces LPS induced: - coagulation activation and fibrinolysis (TAT, DDimer, PAP, etc.) - platelet activation and aggregation (PF4, Whole blood aggregometry, Verify now, etc.) - endothelial activation (vWF activity, endothelial glycocalyx thickness etc.) - cell counts and subsets of monocytes effects of endotoxemia on: platelet proteasome, neutrophil patterns (facs), platelet activation and LPS washout effects ;Primary end point(s): prothrombin fragments F1+2;Timepoint(s) of evaluation of this end point: repeated measures between two study periods (placebo vs. vorapaxar, crossover study) two to four hours after lps bolus usually highest values of prothrombin fragments F1+2 are measured. Thus, main effects will be measured at that time point. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -coagulation activation and fibrinolysis (TAT, PAP, tpa, thrombelastometry etc.) - platelet activation and aggregation (PF4, Whole blood aggregometry, Verify now, proteasome etc.) - inflammation and endothelial activation (endothelial glycocalyx, vWF, etc., TSP-1) - cell counts and monocyte/neutrophil subsets;Timepoint(s) of evaluation of this end point: -24h as baseline 0h before LPS, but 24h after vorapaxar 1h 1,5h 2h 4h 6h 8h 24h after LPS infusion | — |
Countries
Austria
Contacts
Public ContactDept. of Clinical Pharmacology
Medical University of Vienna
Outcome results
None listed