There are two separate objectives in this study: 1. 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 2. To demonstrate the PD profile when participants treated with cangrelor are switched to oral clopidogrel 600 mg administered during or immediately after cangrelor infusion.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
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.
Clopidogrel 600 mg single oral dose
Prasugrel 60 mg single oral dose
Fletcher Allen Health Care
Burlington, Vermont, United States
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).
Time frame: 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).
Time frame: 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
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.
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Time frame: 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.
Time frame: 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.
Time frame: Screening through the follow-up period (5 to 7 days after Day 1)