Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease (SWAP-2)

A Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease: 2nd Switching Antiplatelet Agents

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)..

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Prasugrel Maintenance Dose; Drug: Ticagrelor Maintenance Dose; Drug: Prasugrel Loading Dose

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, B52 8HW
    • Bristol Heart Institute
  • Leicester, United Kingdom, LE3 9QP
    • University Hospital Leicester
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
  • Cardiff
    • Heath Park, Cardiff, United Kingdom, CF14 4XW
      • University Hospital of Wales
• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ. of Florida College Medicine
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology Unit of Miami
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Center for Thrombosis Research
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Medpace Clinical Pharmacology Unit
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Cardiovascular Research
  • Texas
    • Houston, Texas, United States, 77094
      • West Houston Area Clinical Trial Consultants
    • Katy, Texas, United States, 77450
      • Cardiology Center of Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel Maintenance Dose; Prasugrel 10 mg QD MD	Drug: Prasugrel Maintenance Dose; 10mg maintenance dose, given as one 10mg film coated tablet; Other Names: Effient
Active Comparator: Ticagrelor Maintenance Dose; Ticagrelor 90 mg twice-daily (BID) MD	Drug: Ticagrelor Maintenance Dose; one 90mg film coated tablet; Other Names: Brilinta
Experimental: Prasugrel Loading Dose; Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)	Drug: Prasugrel Maintenance Dose; 10mg maintenance dose, given as one 10mg film coated tablet; Other Names: Effient; Drug: Prasugrel Loading Dose; 60mg given as six 10mg film coated tablets; Other Names: Effient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P2Y12 Reaction Units	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.	7 days after first randomized dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P2Y12 Reaction Units	P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment	2, 4, 24, 48 hours after first randomized dose
Platelet Reactivity Index	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.	2, 4, 24, 48 hours, 7 days after first randomized dose
PRU Percent Inhibition (Device-reported)	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.	2, 4, 24, 48 hours, 7 days after first randomized dose
PRU Percent Inhibition (Calculated)	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.	2, 4, 24, 48 hours, 7 days after first randomized dose
Percentage of Subjects With High On-treatment Platelet Reactivity	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	2, 4, 24, 48 hours, 7 days after first randomized dose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: April 26, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimate): April 30, 2012

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2018
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: prasugrel; ticagrelor; CAD; antiplatelet; thienopyridine; P2Y12 Inhibitors
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; 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: CS747s-B-U4003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR