NCT02875028

Vorapaxar in the Human Endotoxemia Model

Vorapaxar in the Human Endotoxemia Model A Randomized, Double-Blind, Crossover Study

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Medical University of Vienna · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	Vorapaxar	10mg-20mg vorapaxar to achieve \>80% thrombin-receptor activated peptide-6 (TRAP) induced platelet inhibition
DRUG	Placebo
OTHER	LPS	2ng/kg Lipopolysaccharide as a bolus infusion

Timeline

• Start date: 2016-06-01
• Primary completion: 2016-11-30
• Completion: 2016-11-30
• First posted: 2016-08-23
• Last updated: 2020-01-10
• Results posted: 2020-01-10

Locations

1 site across 1 country: Austria