Cangrelor to Clopidogrel or Prasugrel Transition Study

Study Overview
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Brief Summary
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There are two separate objectives in this study: To demonstrate the pharmacodynamic (PD) profile when participants treated with cangrelor are switched to oral prasugrel 60 mg administered 30 minutes (min) after cangrelor infusion is discontinued To demonstrate the PD profile when participants treated with cangrelor are switched to oral clopidogrel 600 mg administered during or immediately after cangrelor infusion.

Official Title
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A Study of the Transition From Cangrelor to Clopidogrel or Prasugrel in Patients With Coronary Artery Disease.

Conditions
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Coronary Artery Disease (CAD)

Intervention / Treatment
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* Drug: Cangrelor
* Drug: Clopidogrel
* Drug: Prasugrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Greater than or equal to 18 and less than 75 years of age, of either sex, and of any race. Stable CAD defined by the following criteria: Previous myocardial infarction defined by admission to the hospital with elevation of markers of injury or the presence of pathologic Q-waves on at least 2 contiguous electrocardiogram (ECG) leads. or Previous revascularization by percutaneous coronary intervention or coronary artery bypass graft, and Treatment with aspirin 81 mg daily. Exclusion Criteria: Known intolerance or contraindication to cangrelor or prasugrel, or any ingredients of the respective formulation. Any antiplatelet (other than aspirin) or anticoagulant medication within the previous 30 days. Acute coronary syndrome within the previous 12 months. History of bleeding diathesis or known coagulopathy such as; impaired hemostasis; known international normalized ratio (INR) >1.5; past or present bleeding disorder (including congenital bleeding disorders, such as, von Willebrand's disease or hemophilia), acquired bleeding disorders, and unexplained clinically significant bleeding disorders; thrombocytopenia (platelet count less than 100,000/microliter [µL]), or history of thrombocytopenia or neutropenia associated with clopidogrel. Anemia (for example, hematocrit less than 35%). Prior stroke (any type), prior cerebral arteriovenous malformation or intracranial aneurysm; recent (<1 month) trauma or major surgery (including bypass surgery). Known or suspected pregnancy, or lactating females. Known severe renal insufficiency (glomerular filtration rate less than 30 milliliter [mL]/min). Inability to provide informed consent. Moderate or severe hepatic impairment as per Investigator's discretion (elevation of liver function tests). Inability to swallow oral medication at time of randomization. Any clinically significant disease or condition affecting a major organ system, including but not limited to gastrointestinal, renal, hepatic, endocrinologic, broncho-pulmonary, neurological, or metabolic disease. Any surgical or medical condition which, in the judgment of the Investigator, might interfere with the pharmacokinetics, distribution, metabolism, or excretion of the study drug (if applicable). Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives, whichever is longer, prior to the administration of the drug, or planned use of investigational medicinal products or devices. Participants who, for any reason, are deemed by the Investigator to be inappropriate for this study, including participants who are unable to communicate or to cooperate with the Investigator. Participant is the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study. Active pathological bleeding, or a history of transient ischemic attack.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prasugrel 30 Min After Cangrelor<br>Prasugrel 60 milligram (mg) administered orally 30 min after the discontinuation of cangrelor infusion on Day 1 (2.5 hours [hrs] after initiation of cangrelor infusion). | Drug: Cangrelor<br>* Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1.<br>Drug: Prasugrel<br>* Prasugrel 60 mg single oral dose<br>|
| Experimental: Clopidogrel Within 5 Min After Cangrelor<br>Clopidogrel 600 mg administered orally within 5 min after the discontinuation of the cangrelor infusion on Day 1 (2 hrs after initiation of cangrelor infusion). | Drug: Cangrelor<br>* Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1.<br>Drug: Clopidogrel<br>* Clopidogrel 600 mg single oral dose<br>|
| Experimental: Clopidogrel 1.5 Hrs During Cangrelor<br>Clopidogrel 600 mg administered orally 1.5 hrs after the initiation of cangrelor infusion on Day 1. | Drug: Cangrelor<br>* Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1.<br>Drug: Clopidogrel<br>* Clopidogrel 600 mg single oral dose<br>|
| Experimental: Clopidogrel 1 Hr During Cangrelor<br>Clopidogrel 600 mg administered orally 1 hr after the initiation of cangrelor infusion on Day 1. | Drug: Cangrelor<br>* Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1.<br>Drug: Clopidogrel<br>* Clopidogrel 600 mg single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using light transmittance aggregometry (LTA). LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (sec) (final/terminal aggregation response). | Day 1 at 5.5 or 6 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 2.25, 2.5, 2.75, 3, 4, and 5.5 hrs after initiation of cangrelor infusion | 
| Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | A reference point for cangrelor was chosen for comparison and designated as the administration time of prasugrel 60 mg or clopidogrel 600 mg (2.5, 2, 1.5, or 1 hrs). Platelet function was assessed using LTA. LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was examined using LTA and expressed as % aggregation in response to 20 μM ADP at 300 sec (final/terminal aggregation response). | Day 1 at 1, 1.5, 2, or 2.5 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 1.75 and 2 hrs after initiation of cangrelor infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor to Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone Determined By VerifyNow P2Y12 Assay | A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using the VerifyNow P2Y12 assay. The VerifyNow P2Y12 assay measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was assessed by platelet reaction units (PRU), determined by the VerifyNow P2Y12 assay. The VerifyNow P2Y12 assay is designed to directly measure the effects of drugs on the P2Y12 receptor, using prostaglandin E1 in addition to ADP to increase intraplatelet cyclic adenosine monophosphate (cAMP). Platelet reactivity was expressed in PRU. | Day 1 at 5.5 or 6 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 2.25, 2.5, 2.75, 3, 4, and 5.5 hrs after initiation of cangrelor infusion | 
| Extent of Preservation of Platelet Inhibitory Effect of Cangrelor Treatment After Prasugrel or Clopidogrel Compared to Treatment With Cangrelor Alone Determined By VerifyNow P2Y12 Assay | A reference point for cangrelor was chosen for comparison and designated as the administration time of prasugrel 60 mg or clopidogrel 600 mg (2.5, 2, 1.5, or 1 hrs). Platelet function was assessed using the VerifyNow P2Y12 assay. The VerifyNow P2Y12 assay measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was assessed by PRU, determined by the VerifyNow P2Y12 assay. The VerifyNow P2Y12 assay is designed to directly measure the effects of drugs on the P2Y12 receptor, using prostaglandin E1 in addition to ADP to increase intraplatelet cAMP. Platelet reactivity was expressed in PRU. | Day 1 at 1, 1.5, 2, or 2.5 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 1.75 and 2 hrs after initiation of cangrelor infusion | 
| Bleeding Events In Accordance With GUSTO Scale | Bleeding was assessed by history, physical exam, and complete blood count (CBC) that was performed on study Day 1. Reports of bleeding were to be evaluated by performance of a CBC. Participants were assessed for bleeding events in accordance with the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) scale. The severity of bleeding events by GUSTO Criteria is defined as the following: Severe/life-threatening: fatal, intracranial hemorrhage, or if hemodynamic compromise results Moderate: transfusion required Mild: no transfusion or hemodynamic compromise A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Screening through the follow-up period (5 to 7 days after Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAD