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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01587651
First received: April 26, 2012
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Coronary Artery Disease
Drug: Prasugrel Loading Dose
Drug: Prasugrel Maintenance Dose
Drug: Ticagrelor Maintenance Dose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • P2Y12 Reaction Units [ Time Frame: 7 days after first randomized dose ] [ Designated as safety issue: No ]
    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:
  • P2Y12 Reaction Units [ Time Frame: 2, 4, 24, 48 hours after first randomized dose ] [ Designated as safety issue: No ]
    P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment

  • Platelet Reactivity Index [ Time Frame: 2, 4, 24, 48 hours, 7 days after first randomized dose ] [ Designated as safety issue: No ]

    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 (Device-reported) [ Time Frame: 2, 4, 24, 48 hours, 7 days after first randomized dose ] [ Designated as safety issue: No ]

    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.


  • PRU Percent Inhibition (Calculated) [ Time Frame: 2, 4, 24, 48 hours, 7 days after first randomized dose ] [ Designated as safety issue: No ]

    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.


  • Percentage of Subjects With High On-treatment Platelet Reactivity [ Time Frame: 2, 4, 24, 48 hours, 7 days after first randomized dose ] [ Designated as safety issue: No ]

    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



Enrollment: 110
Study Start Date: March 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01587651

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

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01587651     History of Changes
Other Study ID Numbers: CS747s-B-U4003
Study First Received: April 26, 2012
Results First Received: February 11, 2014
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration

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
Platelet Aggregation Inhibitors
Prasugrel
Ticagrelor
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014