A Single Center Study to Evaluate Ticagrelor Mechanism of Action in Inhibiting Juvenile Platelet ADP Response

A Single Center, Randomized, Open Label, Crossover Study With Ticagrelor and Prasugrel to Evaluate Ticagrelor Mechanism of Action in Inhibiting Juvenile Platelet ADP Response

The overall objective of this study is to assess P2Y12 inhibition ex vivo in blood samples obtained from diabetic subjects who will be administered one of the two P2Y12 antagonists in a cross-over design.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Ticagrelor; Drug: Prasugrel

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Male or female aged 18 to 70 years, inclusive.
3. Documented current medical history of diabetes controlled by either medication or diet and/or exercise.
4. Women must have a negative urine pregnancy test.

Exclusion Criteria:

1. Pregnant or lactating females, or females of child-bearing potential (i.e., those who are not chemically or surgically sterilized or who are not post-menopause) or those who are not willing to use a medically accepted method of contraception that is considered reliable in the judgement of the investigator throughout the duration of the study or females who have a positive pregnancy test at screening.
2. Weight of less than 135 lbs.
3. Currently prescribed and taking clopidogrel (generic or Plavix), ticagrelor (Brilinta) or prasugrel (Effient) or have taken within the past 10 days.

4. Current medications:

   1. PAR-1 antagonist (vorapaxar/Zontivity) or within the last month.
   2. Phosphodiesterase inhibitors such as cilostazol (Pletal).
   3. Glycoprotein IIb/IIIa inhibitors or within the last ten days (Integrilin, Aggrastat, ReoPro).
   4. Adenosine reuptake inhibitors such as dipyridamole (Aggrenox, Persantine)
   5. Coumadin.
   6. Heparin including low molecular weight heparin.
   7. Factor Xa inhibitors (e.g., enoxaparin, rivaroxaban, apixaban, and edoxaban).
   8. Direct thrombin inhibitors (e.g., hirudin, bivalirudin, dabigatran.
   9. Concomitant therapy with strong CYP3A inhibitors, such as atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazadone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconizole,
   10. Concomitant therapy with potent CYP3A inducers, such as rifampin, phenytoin, carbamazepine, and phenobarbital.

5. Increased bleeding risk including:

   1. Recent (within 30 days) GI bleeding
   2. Active pathological bleeding
   3. Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding
   4. Prior history of transient ischemic attack or stroke
   5. Recent (within 3 months) major trauma
   6. Sustained uncontrolled hypertension (systolic blood pressure [SBP] > 180mmHg or diastolic blood pressure [DBP] > 100mmHg
   7. History of hemorrhagic disorders that can increase the risk of bleeding (e.g., hemophilia, von Willebrand's disease)
   8. Patients that have used within 30 days of screening, any oral or parenteral anti-thrombotic agent.
   9. Platelet count less than 100,000 mm3 or hemoglobin < 10g/dL
6. Contraindication or other reason that ticagrelor or prasugrel should not be administered (e.g., known hypersensitivity to medication or any medication component)
7. A history of alcohol and/or substance abuse that could interfere with conduct of the trial.
8. Known active or recurrent hepatic disorder (including cirrhosis, hepatitis B and hepatitis C, or confirmed (ALT/AST) levels > 3 times ULN or total bilirubin > 2 times ULN at screening.
9. Scheduled for revascularization (e.g., PCI, CABG) during the study period.
10. Any Acute Coronary Syndrome (ACS) event within the past 6 months.
11. Participation in another investigational drug or device study within 30 days of dosing.
12. Any acute or chronic unstable condition in the past 30 days or other condition which, in the opinion of the investigator, may either put the subject at risk or influence the result of the study (e.g., active cancer, risk for non-compliance, risk for lost to follow-up).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group 2	Drug: Ticagrelor; Ticagrelor, 90mg twice daily; Other Names: Brilinta; Drug: Prasugrel; Prasurgrel, 10mg once daily; Other Names: Effient
ACTIVE_COMPARATOR: Group 1	Drug: Ticagrelor; Ticagrelor, 90mg twice daily; Other Names: Brilinta; Drug: Prasugrel; Prasurgrel, 10mg once daily; Other Names: Effient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aggregation Response	Comparison of aggregation response using ADP in subjects receiving prasurgrel versus ticagrelor	23 hr Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reticulated Platelet Reactivity Index (PRI)	Comparison of PRI as measured by VASP in subjects receiving ticagrelor versus subjects receiving prasugrel	23 hr Day 5

Collaborators and Investigators

• Sponsor: CirQuest Labs, LLC
• Investigators: Principal Investigator: Jayaprakash Kotha, CirQuest Labs

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 28, 2017
• Primary Completion (ANTICIPATED): October 31, 2017
• Study Completion (ANTICIPATED): October 31, 2017

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: January 18, 2017
• First Posted (ESTIMATE): January 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: ESR-14-10619

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No