Impact of Anti-platelet Drug Exposure on Platelet mRNA Splicing in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this pilot study is to determine how the anti-platelet drug, ticagrelor, impacts platelet mRNA splicing after a single loading dose in 10 healthy participants. These results will be valuable in that they will help inform our analysis of platelet RNA splicing after a thrombotic event.

Detailed Description
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There is nothing known on how differential splicing in platelets is impacted by of P2Y12 inhibition by anti-platelet agents. Consequently, the focus of this longitudinal pilot study will be to determine the impact of a single ticagrelor loading dose (180 mg), our model anti-platelet drug, on platelet RNA splicing in 10 healthy individuals. It will test the hypothesis that ticagrelor exposure does not significantly alter platelet mRNA splicing. It will involve administering a single loading dose (180 mg) of ticagrelor to healthy volunteers.

Official Title
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Investigation of Anti-platelet Drug Single Dose Exposure on Platelet mRNA Splicing in Healthy Subjects

Conditions
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Thrombosis; Artery

Intervention / Treatment
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* Drug: Ticagrelor Oral Tablet [Brilinta]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 70 years-old Speak and understand English Exclusion Criteria: History of blood clotting/bleeding disorders Current medications that are CYP3A4 inhibitors/inducers Current medications that their pharmacokinetics is impacted by ticagrelor (i.e. simvastatin, lovastatin, digoxin) per FDA recommendations. Diagnosed with arterial or venous thrombosis Active cancer diagnosis Pregnant Hepatic impairment including active hepatitis infection or cirrhosis Current hormonal contraception Currently taking aspirin or anti-platelet drugs. If patient has recently taken an NSAID, the last dose should have been discontinued based established criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Patients<br>The study design will involve analysis of platelet splicing/activity before and after exposure to a single, 180 mg loading dose of ticagrelor. All subjects will be cardiovascular healthy. | Drug: Ticagrelor Oral Tablet [Brilinta]<br>* A single loading dose of ticagrelor (180 mg) will be administered to each participant in this study.<br>* Other names: Brilinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the Change in Platelet Activity From Baseline after Drug Administration | As determined by the VerifyNow P2Y12 Assay | Comparison made 2.5 hours following drug administration | 
| Measurement of the Change in Platelet mRNA splicing From Baseline after Drug Administration | As determined by RNAseq analysis | Comparison made 2.5 hours following drug administration | 
| Measurement of Ticagrelor Pharmacokinetics After Drug Administration | Drug and its major metabolite levels will be measured by HPLC | Comparison made 2.5 hours following drug administration |