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

Withdrawn

• Conditions: Thrombosis; Artery
• Interventions: Drug: Ticagrelor Oral Tablet [Brilinta]

• Registration Number: NCT04088123
• Lead Sponsor: George Washington University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-09-10
• Study First Submitted QC: 2019-09-11
• Study First Posted: 2019-09-12
• Study Start: 2020-04-01
• Primary Completion: 2020-09-23
• Study Completion: 2020-09-23
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-21
• Last Update Posted: 2021-10-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Patients	Ticagrelor Oral Tablet [Brilinta]	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.

Primary Outcome Measures

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

Trial Locations

Locations (2)

The George Washington University School of Medicine and Health Sciences; 🇺🇸 Washington, District of Columbia, United States

Shenandoah University Bernard J. Dunn School of Pharmacy; 🇺🇸 Fairfax, Virginia, United States