Effect of Free Ticagrelor Fraction on Platelet Membrane Post MI

Study Overview
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Brief Summary
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The purpose of this study is to assess: the population pharmacokinetics of unbound ticagrelor and its metabolite in acute coronary syndrome patients treated by ticagrelor ticagrelor and its metabolite levels by LC-MS/MS

Detailed Description
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Ticagrelor is an anti-platelet agent of the cyclopentyltriazolopyrimidine class. It is administered by the oral route, rapidly absorbed (2-3 hours), and has a bio-availability estimated at around 36%. Contrary to other P2Y12 inhibitors, ticagrelor is not a pro-drug and does not need to be metabolized to exert is pharmacodynamic effect. It had been previously showed that stimulation of platelets by ADP or inhibitors of platelets by ticagrelor modified the organisation of the platelet membrane, with a re-distribution of cholesterol and P2Y12 receptors towards the lipid rafts. This suggests that lipid membranes and cholesterol may play an important role in the anti-platelet activity of ticagrelor. In this context, the aim of the study is to assess: the population pharmacokinetics of unbound ticagrelor and its metabolite in acute coronary syndrome patients treated by ticagrelor ticagrelor and its metabolite levels by LC-MS/MS.

Official Title
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Population-Based Pharmacokinetic / Pharmacodynamic Modeling of the Effect of Free Ticagrelor Fraction on the Platelet Membrane in Post Myocardial Infarction Patients

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Other: Blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged over 18 years and less than 90 years, Patients admitted for myocardial infarction treated with ticagrelor in association with aspirin. Patients affiliated to a social security system (or be a beneficiary thereof); Sign written informed consent indicating that they have understood the study procedures and objectives, and that they accept to participate and adhere to the study requirements. Exclusion Criteria: Patients with limited legal capacity or patients under legal guardianship Patients under judicial protection Patients not affiliated to any social security system Patients taking any antiplatelet agent other than ticagrelor Patients taking ticagrelor for <48 hours (treatment not stabilised) Patients with hemoglobin concentration <10 g/dL on the most recent blood test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study cohort<br>Adult (>18 years, <90 years) patients admitted and treated for acute myocardial infarction, and whose treatment includes ticagrelor in association with aspirin. Blood samples will be taken at 3 timepoints between two doses of ticagrelor (taken at 12 hours interval). | Other: Blood sample<br>* 3 blood samples, for a maximum of 60mL, will be taken at 0-3h, 3-6h and >6h, between two doses of ticagrelor (taken at 0 and 12 hours).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| concentration of unbound ticagrelor and its metabolite | Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin | at 3 hours after administration of the first dose of ticagrelor | 
| concentration of unbound ticagrelor and its metabolite | Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin | at 6 hours after administration of the first dose of ticagrelor | 
| concentration of unbound ticagrelor and its metabolite | Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin | at 12 hours after administration of the first dose of ticagrelor | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the method of determination of ticagrelor concentration | Identify the optimum settings for the measurement of the concentration of ticagrelor (total and free fraction) and its active metabolite in the plasma by LC-MS/MS | at 3 hours after administration of the first dose of ticagrelor | 
| Assess the method of determination of ticagrelor concentration | Identify the optimum settings for the measurement of the concentration of ticagrelor (total and free fraction) and its active metabolite in the plasma by LC-MS/MS | at 6 hours after administration of the first dose of ticagrelor | 
| Assess the method of determination of ticagrelor concentration | Identify the optimum settings for the measurement of the concentration of ticagrelor (total and free fraction) and its active metabolite in the plasma by LC-MS/MS | at 12 hours after administration of the first dose of ticagrelor | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ticagrelor, acute coronary syndrome, anti-platelet drug