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

• ClinicalTrials.gov Identifier: NCT01587651
• Recruitment Status: Completed
• First Posted: April 30, 2012
• Results First Posted: April 29, 2014
• Last Update Posted: January 9, 2019
• Sponsor: Daiichi Sankyo, Inc.
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Study Description

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)..

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: Prasugrel Loading Dose; Drug: Prasugrel Maintenance Dose; Drug: Ticagrelor Maintenance Dose	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease: 2nd Switching Antiplatelet Agents
• Study Start Date: March 2012
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: February 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. P2Y12 Reaction Units [ Time Frame: 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 :

1. P2Y12 Reaction Units [ Time Frame: 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
2. Platelet Reactivity Index [ Time Frame: 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.

3. PRU Percent Inhibition (Device-reported) [ Time Frame: 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.

4. PRU Percent Inhibition (Calculated) [ Time Frame: 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.

5. Percentage of Subjects With High On-treatment Platelet Reactivity [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Univ. of Florida College Medicine

Jacksonville, Florida, United States, 32209

Clinical Pharmacology Unit of Miami

Miami, Florida, United States, 33014

Progressive Medical Research

Port Orange, Florida, United States, 32127

United States, Maryland

Sinai Center for Thrombosis Research

Baltimore, Maryland, United States, 21215

United States, Ohio

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, United States, 45212

United States, South Dakota

Black Hills Cardiovascular Research

Rapid City, South Dakota, United States, 57701

United States, Texas

West Houston Area Clinical Trial Consultants

Houston, Texas, United States, 77094

Cardiology Center of Houston

Katy, Texas, United States, 77450

United Kingdom

University Hospital of Wales

Heath Park, Cardiff, United Kingdom, CF14 4XW

Bristol Heart Institute

Bristol, United Kingdom, B52 8HW

University Hospital Leicester

Leicester, United Kingdom, LE3 9QP

Southampton General Hospital

Southampton, United Kingdom, SO16 6YD

New Cross Hospital

Wolverhampton, United Kingdom, WV10 0QP

Sponsors and Collaborators

Daiichi Sankyo, Inc.

Eli Lilly and Company

More Information

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01587651
• Other Study ID Numbers: CS747s-B-U4003
• First Posted: April 30, 2012
• Results First Posted: April 29, 2014
• Last Update Posted: January 9, 2019
• Last Verified: March 2014

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

Keywords provided by Daiichi Sankyo, Inc.:

CAD; prasugrel; ticagrelor; antiplatelet; thienopyridine; P2Y12 Inhibitors

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Ticagrelor; Prasugrel Hydrochloride; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs