Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease

Phase 4

Completed

Conditions: Coronary Artery Disease

Interventions: Drug: Prasugrel Maintenance Dose
Drug: Ticagrelor Maintenance Dose
Drug: Prasugrel Loading Dose

Registration Number: NCT01587651

Lead Sponsor: Daiichi Sankyo

Brief Summary: This is a Phase 4, multicenter, open-label (blinded Pharmacodynamic PD results), randomized, 3-arm, parallel-design study of subjects with stable Coronary Artery Disease CAD. This study will compare the PD effect of prasugrel 10 mg QD (once-daily) maintenance dose with ticagrelor 90 mg BID (twice daily) maintenance dose in subjects with stable CAD who have previously received ticagrelor loading does (LD) and maintenance dose (MD)..

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

Inclusion Criteria

Male or female; age >= 18 and < 75 years
Weight >= 60 kg
Receiving low dose ASA (75 mg to 150 mg daily) for at least 7 days at the time of Visit 1 and able to continue the same regimen throughout the study
Stable CAD. CAD is defined as any of the following:
History of a positive stress test
Previous coronary revascularization including percutaneous coronary intervention (PCI), stent, or coronary artery bypass graft (CABG)
Angiographic demonstration of CAD (at least

1 lesion >= 50 percent)
Presence of at least moderate plaque by computed tomography (CT) angiography
Electron beam CT coronary artery calcification score >= 100 Agatston units
If female, may be enrolled if

One of the following 3 criteria are met:

Had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form (ICF)
Post-menopausal for at least 1 year
If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy
Able and willing to provide written informed consent before entering the study

Exclusion Criteria

Have a defined need for adenosine diphosphate (ADP)-receptor inhibitor therapy, such as any of the following (or any other condition that in the Investigator's judgment would require such therapy):
Within =< 12 months of an acute coronary syndrome (ACS) event (unstable angina [UA], non-ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]) regardless of initial treatment (that is, invasive versus noninvasive)
Subjects who underwent angioplasty within 12 months including bare-metal stent and/or a drug-eluting stent
Had any stent placed in an unprotected left main coronary artery or in the last patent artery within the last 12 months
Received thienopyridine therapy within 30 days of study entry
Plan to undergo coronary revascularization at any time during the trial
Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry)
History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope)
History or evidence of congestive heart failure (New York Heart Association Class III or above =< 6 months before screening
Severe hepatic impairment
History of uric acid nephropathy
Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening
Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on dialysis
At risk for bleeding
Taking prohibited medications

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prasugrel Maintenance Dose	Prasugrel Maintenance Dose	Prasugrel 10 mg QD MD
Ticagrelor Maintenance Dose	Ticagrelor Maintenance Dose	Ticagrelor 90 mg twice-daily (BID) MD
Prasugrel Loading Dose	Prasugrel Loading Dose	Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)
Prasugrel Loading Dose	Prasugrel Maintenance Dose	Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)

Primary Outcome Measures

Name	Time	Method
P2Y12 Reaction Units	7 days after first randomized dose	P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. Platelet aggregation with this system is defined by PRU, with a higher PRU indicative of greater platelet aggregation, and a lower PRU indicative of inhibition.

Secondary Outcome Measures

Name	Time	Method
Platelet Reactivity Index	2, 4, 24, 48 hours, 7 days after first randomized dose	Platelet Reactivity Index (PRI) by the Vasodilator-Stimulated Phosphoprotein(VASP) assay 2, 4, 24, 48 hours and 7 days after first randomized study treatment. The VASP assay is an indirect, but relatively specific measure of inhibition of P2Y12-induced platelet activation. The assay quantifies the level of phosphorylation of the intracellular protein VASP, which undergoes phosphorylation when platelet P2Y12 receptors are blocked. The level of VASP phosphorylation, expressed as the PRI, represents the percentage inhibition relative to an assay baseline/maximal P2Y12-independent platelet aggregation.
PRU Percent Inhibition (Calculated)	2, 4, 24, 48 hours, 7 days after first randomized dose	Analysis of Mean Calculated Percent Inhibition by time point Calculated percent inhibition at time point t is defined as: 100 × (baseline PRU - PRUt)/baseline PRU where baseline PRU is the VerifyNow PRU value at pre-run-in baseline and PRUt is the VerifyNow PRU value at time t.
P2Y12 Reaction Units	2, 4, 24, 48 hours after first randomized dose	P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment
PRU Percent Inhibition (Device-reported)	2, 4, 24, 48 hours, 7 days after first randomized dose	PRU VerifyNow P2Y12 assay device-reported percent inhibition 2, 4, 24, and 48 hours, and 7 days after first randomized study treatment VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. The percent inhibition reported by VerifyNow device represents the percentage inhibition relative to maximal P2Y12-independent platelet aggregation achieved with the same sample in the presence of the iso-thrombin receptor activating peptide.
Percentage of Subjects With High On-treatment Platelet Reactivity	2, 4, 24, 48 hours, 7 days after first randomized dose	Percentage of subjects with High on-treatment Platelet Reactivity (HPR) defined as a) \>= 208 PRU and b) \>= 230 PRU by the VerifyNow P2Y12 assay and c) \>50% PRI by the VASP assay, 2, 4, 24, and 48 hours and 7 days after first randomized study treatment. A poor response of the platelets to "drug", called High Residual Platelet Reactivity (HRPR), has been incriminated to account for a recurrence of ischemic events

Trial Locations

Locations (13): Sinai Center for Thrombosis Research
🇺🇸
Baltimore, Maryland, United States
Clinical Pharmacology Unit of Miami
🇺🇸
Miami, Florida, United States
Medpace Clinical Pharmacology Unit
🇺🇸
Cincinnati, Ohio, United States
West Houston Area Clinical Trial Consultants
🇺🇸
Houston, Texas, United States
University Hospital of Wales
🇬🇧
Heath Park, Cardiff, United Kingdom
Black Hills Cardiovascular Research
🇺🇸
Rapid City, South Dakota, United States
Univ. of Florida College Medicine
🇺🇸
Jacksonville, Florida, United States
New Cross Hospital
🇬🇧
Wolverhampton, United Kingdom
University Hospital Leicester
🇬🇧
Leicester, United Kingdom
Progressive Medical Research
🇺🇸
Port Orange, Florida, United States
Bristol Heart Institute
🇬🇧
Bristol, United Kingdom
Cardiology Center of Houston
🇺🇸
Katy, Texas, United States
Southampton General Hospital
🇬🇧
Southampton, United Kingdom