Vorapaxar in the Human Endotoxemia Model

NCT02875028 | Completed Phase 4 Results

• 1 other identifier: LPS_Vorapaxar_1.1
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Vorapaxar is a recently approved protease activated receptor - 1 (PAR-1) inhibitor. Platelet inhibition may also exert positive results on coagulation activation and may beneficially influence the inflammatory response. Since vorapaxar is the first available substance of a new class of platelet inhibitors its effects on the human coagulation system and the inflammatory response will be assessed in the well-established human endotoxemia model.

Conditions

Healthy Volunteers

Keywords

Coagulations; Platelets; Inflammation; endotoxemia; vorapaxar

Outcome Measures

Primary Outcomes (1)

• Changes in Prothrombin Fragments F1+2

  prothrombin fragment F1+2 concentrations, individual maxima were compared between both study periods

  Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h

Secondary Outcomes (11)

• Protease Activated Receptor (PAR)-1 Expression on Platelets

  Time points for evaluation were: baseline, 0h, 4h, 24h

• Thrombin-Antithrombin Complexes

  Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h

• Plasmin-Antiplasmin Complexes

  Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h

• E-Selectin

  Time points for evaluation were baseline, 2h, 4h, 6h, 24h after LPS administration

• Von Willebrand Factor

  Time points for evaluation were baseline, 2h, 4h, 6h, 24h after LPS administration

Study Arms (2)

Vorapaxar

EXPERIMENTAL

subjects will be treated with 4x2,5mg vorapaxar in empty lactose-starch capsules

Drug: Vorapaxar; Other: LPS

Placebo

PLACEBO COMPARATOR

subjects will be treated with 4 empty lactose-starch capsules

Drug: Placebo; Other: LPS

Interventions

Vorapaxar DRUG

10mg-20mg vorapaxar to achieve \>80% thrombin-receptor activated peptide-6 (TRAP) induced platelet inhibition

Vorapaxar

Placebo DRUG

Also known as: capsules consisting of lactose-starch

Placebo

LPS OTHER

2ng/kg Lipopolysaccharide as a bolus infusion

Also known as: Lipopolysaccharide

Placebo; Vorapaxar

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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

You may not qualify if:

• Intake of any drugs that may interfere with the trial's endpoints or drugs (i.e. platelet inhibitors, anticoagulants, CYP3A4 inhibitors, NSAIDs, selective serotonin reuptake inhibitors, selective noradrenaline and serotonin reuptake inhibitors)
• 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
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Inflammation; Endotoxemia

Interventions

vorapaxar; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Bernd Jilma
• Organization: Medical University of Vienna

bernd.jilma@meduniwien.ac.at

+4314040029910

Study Officials

• Bernd Jilma, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ao.Univ.Prof.Dr.med

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: August 23, 2016
• Study Start: June 1, 2016
• Primary Completion: November 30, 2016
• Study Completion: November 30, 2016
• Last Updated: January 10, 2020
• Results First Posted: January 10, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)