Vorapaxar in the Human Endotoxemia Model

NCT ID: NCT02875028

Last Updated: 2020-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2016-11-30

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.

Detailed Description

Vorapaxar is a novel platelet inhibitor inhibiting PAR-1. It is the first available substance of a new class of platelet inhibitors blocking the activation of platelets via thrombin or thrombin receptor activating peptides via PAR-1. As platelets contribute to the coagulation activation, i.e. by providing the surface for the assembly of the Tenase complex, and furthermore to the inflammatory response by releasing their stored granula containing promotors of both, inflammation and coagulation, we want to assess the effects of vorapaxar on these in the human endotoxemia model. Sixteen healthy volunteers will be included in this randomized, double-blind, placebo-controlled, single center, crossover trial with a washout period of 8 weeks. This wash out period was chosen based on the long elimination half-life of vorapaxar and to prevent any carry-over effects. After intake of 10mg vorapaxar (-24h) the degree of platelet inhibition will be assessed by whole bood aggregometry and, in case of insufficient platelet inhibition, subjects may receive another 10mg of vorapaxar. A bolus of 2ng/kg bodyweight lipopolysaccharide (LPS) will be infused and blood sampling will be performed at pre-defined time-points. After the washout-period the respective other treatment will be given to subjects.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vorapaxar

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

Group Type: EXPERIMENTAL

Vorapaxar

Intervention Type: DRUG

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

LPS

Intervention Type: OTHER

2ng/kg Lipopolysaccharide as a bolus infusion

Placebo

subjects will be treated with 4 empty lactose-starch capsules

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

LPS

Intervention Type: OTHER

2ng/kg Lipopolysaccharide as a bolus infusion

Interventions

Vorapaxar

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

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

LPS

2ng/kg Lipopolysaccharide as a bolus infusion

Intervention Type: OTHER

Other Intervention Names

capsules consisting of lactose-starch; Lipopolysaccharide

Eligibility 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Bernd Jilma

Ao.Univ.Prof.Dr.med

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bernd Jilma, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

LPS_Vorapaxar_1.1

Identifier Type: -

Identifier Source: org_study_id