Effect of Free Ticagrelor Fraction on Platelet Membrane Post MI (PLATIME)

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Other: Blood sample

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Jennifer Lagoutte-Renosi, MPharm; Phone Number: +33370632379; Email: jlagoutte@chu-besancon.fr

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CHU Besançon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the Cardiology department with a main diagnosis of acute coronary syndrome and treated with a treatment combination including ticagrelor and aspirin.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study cohort; 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; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besançon
• Investigators: Principal Investigator: Nicolas Meneveau, MD, PhD, Dept of Cardiology, CHU Besancon

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2019
• Primary Completion (Anticipated): April 9, 2022
• Study Completion (Anticipated): April 9, 2022

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: September 3, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Ticagrelor; acute coronary syndrome; anti-platelet drug
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome
• Other Study ID Numbers: P/2018/371

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No