Coronary Artery Disease (CAD)
Conditions
Keywords
CAD
Brief summary
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.
Interventions
DRUGCangrelor
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.
DRUGClopidogrel
Clopidogrel 600 mg single oral dose
DRUGPrasugrel
Prasugrel 60 mg single oral dose
Sponsors
The Medicines Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Greater than or equal to 18 and less than 75 years of age, of either sex, and of any race. 2. Stable CAD defined by the following criteria: 1. 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 2. Previous revascularization by percutaneous coronary intervention or coronary artery bypass graft, and 3. Treatment with aspirin 81 mg daily.
Exclusion criteria
1. Known intolerance or contraindication to cangrelor or prasugrel, or any ingredients of the respective formulation. 2. Any antiplatelet (other than aspirin) or anticoagulant medication within the previous 30 days. 3. Acute coronary syndrome within the previous 12 months. 4. 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. 5. Anemia (for example, hematocrit less than 35%). 6. Prior stroke (any type), prior cerebral arteriovenous malformation or intracranial aneurysm; recent (\<1 month) trauma or major surgery (including bypass surgery). 7. Known or suspected pregnancy, or lactating females. 8. Known severe renal insufficiency (glomerular filtration rate less than 30 milliliter \[mL\]/min). 9. Inability to provide informed consent. 10. Moderate or severe hepatic impairment as per Investigator's discretion (elevation of liver function tests). 11. Inability to swallow oral medication at time of randomization. 12. 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. 13. 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). 14. 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. 15. 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. 16. 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. 17. Active pathological bleeding, or a history of transient ischemic attack.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 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 | 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). |
| Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
| 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 | 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 | 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. |
| Bleeding Events In Accordance With GUSTO Scale | Screening through the follow-up period (5 to 7 days after Day 1) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs.
Prasugrel 60 mg was administered on Day 1 as a single oral dose 30 min on Day 1 after the discontinuation of cangrelor infusion. | 3 |
| Clopidogrel Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs on Day 1.
Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1 and 1.5 hrs after the initiation of cangrelor infusion and within 5 min after the discontinuation of the cangrelor infusion. | 12 |
| Total | 15 |
Baseline characteristics
| Characteristic | Prasugrel | Total | Clopidogrel |
|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 6.66 | 64.7 years STANDARD_DEVIATION 6.15 | 65.3 years STANDARD_DEVIATION 6.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 15 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 15 Participants | 12 Participants |
| Region of Enrollment United States | 3 Participants | 15 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 15 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 3 |
Outcome results
Primary
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
Population: Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 3 hrs | 65.0 % aggregation | Standard Deviation 2 |
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 1.3 % aggregation | Standard Deviation 1.5 |
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.5 hrs | 60.0 % aggregation | Standard Deviation 7.5 |
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 4 hrs | 16.3 % aggregation | Standard Deviation 27.4 |
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 5.5 hrs | 1.3 % aggregation | Standard Deviation 1.5 |
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.75 hrs | 63.3 % aggregation | Standard Deviation 1.5 |
| Prasugrel 30 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.25 hrs | 16.3 % aggregation | Standard Deviation 10.1 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.5 hrs | 49.7 % aggregation | Standard Deviation 7.1 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 4 hrs | 38.0 % aggregation | Standard Deviation 31.7 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 5.5 hrs | 26.7 % aggregation | Standard Deviation 20.5 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.25 hrs | 26.0 % aggregation | Standard Deviation 7.9 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.75 hrs | 58.3 % aggregation | Standard Deviation 7.4 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 21.7 % aggregation | Standard Deviation 16.4 |
| Clopidogrel Within 5 Min After Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 3 hrs | 56.0 % aggregation | Standard Deviation 8.9 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 50.0 % aggregation | Standard Deviation 16.8 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.75 hrs | 56.8 % aggregation | Standard Deviation 11.3 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 3 hrs | 56.2 % aggregation | Standard Deviation 16.4 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 4 hrs | 51.2 % aggregation | Standard Deviation 27.4 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.5 hrs | 54.3 % aggregation | Standard Deviation 11.7 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.25 hrs | 22.2 % aggregation | Standard Deviation 16 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 5.5 hrs | NA % aggregation | — |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 5.5 hrs | NA % aggregation | — |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 50.3 % aggregation | Standard Deviation 15.9 |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.5 hrs | 62.0 % aggregation | Standard Deviation 3.6 |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.75 hrs | 67.7 % aggregation | Standard Deviation 1.2 |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 3 hrs | 65.0 % aggregation | Standard Deviation 9.5 |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 4 hrs | 62.7 % aggregation | Standard Deviation 8.5 |
| Clopidogrel 1 Hr During Cangrelor | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone | 2.25 hrs | 33.3 % aggregation | Standard Deviation 7.5 |
Primary
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
Population: Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel 30 Min After Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 60.0 % aggregation | Standard Deviation 7.5 |
| Prasugrel 30 Min After Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 2 hrs | 0.3 % aggregation | Standard Deviation 0.6 |
| Prasugrel 30 Min After Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 1.75 hrs | 0.3 % aggregation | Standard Deviation 0.6 |
| Clopidogrel Within 5 Min After Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 0 % aggregation | Standard Deviation 0 |
| Clopidogrel Within 5 Min After Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 2 hrs | NA % aggregation | — |
| Clopidogrel Within 5 Min After Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 1.75 hrs | 1.0 % aggregation | Standard Deviation 1 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 1.75 hrs | 1.8 % aggregation | Standard Deviation 2.5 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 2.0 % aggregation | Standard Deviation 3.5 |
| Clopidogrel 1.5 Hrs During Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 2 hrs | 1.5 % aggregation | Standard Deviation 2 |
| Clopidogrel 1 Hr During Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 3.0 % aggregation | Standard Deviation 2 |
| Clopidogrel 1 Hr During Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 2 hrs | 2.3 % aggregation | Standard Deviation 1.2 |
| Clopidogrel 1 Hr During Cangrelor | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone | 1.75 hrs | 1.3 % aggregation | Standard Deviation 0.6 |
Secondary
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)
Population: Safety Population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel 30 Min After Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Mild | 0 bleeding events |
| Prasugrel 30 Min After Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Life-threatening/Severe | 0 bleeding events |
| Prasugrel 30 Min After Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Moderate | 0 bleeding events |
| Clopidogrel Within 5 Min After Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Mild | 0 bleeding events |
| Clopidogrel Within 5 Min After Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Life-threatening/Severe | 0 bleeding events |
| Clopidogrel Within 5 Min After Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Moderate | 0 bleeding events |
| Clopidogrel 1.5 Hrs During Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Moderate | 0 bleeding events |
| Clopidogrel 1.5 Hrs During Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Mild | 0 bleeding events |
| Clopidogrel 1.5 Hrs During Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Life-threatening/Severe | 0 bleeding events |
| Clopidogrel 1 Hr During Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Mild | 0 bleeding events |
| Clopidogrel 1 Hr During Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Life-threatening/Severe | 0 bleeding events |
| Clopidogrel 1 Hr During Cangrelor | Bleeding Events In Accordance With GUSTO Scale | Moderate | 0 bleeding events |
Secondary
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.
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
Population: Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel 30 Min After Cangrelor | 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 | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 8.0 PRU | Standard Deviation 8.7 |
| Prasugrel 30 Min After Cangrelor | 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 | 4 hrs | 77.0 PRU | Standard Deviation 126.5 |
| Prasugrel 30 Min After Cangrelor | 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 | 3 hrs | 226.0 PRU | Standard Deviation 28.5 |
| Prasugrel 30 Min After Cangrelor | 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 | 2.25 hrs | 76.7 PRU | Standard Deviation 23.7 |
| Prasugrel 30 Min After Cangrelor | 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 | 5.5 hrs | 24.5 PRU | Standard Deviation 34.6 |
| Prasugrel 30 Min After Cangrelor | 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 | 2.5 hrs | 208.0 PRU | Standard Deviation 30.2 |
| Prasugrel 30 Min After Cangrelor | 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 | 2.75 hrs | 225.7 PRU | Standard Deviation 42.5 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 4 hrs | 182.0 PRU | Standard Deviation 82.3 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 2.75 hrs | 233.0 PRU | Standard Deviation 21.7 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 2.5 hrs | 220.7 PRU | Standard Deviation 11.6 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 3 hrs | 215.7 PRU | Standard Deviation 35 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 5.5 hrs | 155.0 PRU | Standard Deviation 69.8 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 2.25 hrs | 99.0 PRU | Standard Deviation 27.6 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 159.0 PRU | Standard Deviation 72.7 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 2.75 hrs | 255.8 PRU | Standard Deviation 43.7 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 211.3 PRU | Standard Deviation 66.8 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 2.25 hrs | 90.3 PRU | Standard Deviation 32.3 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 2.5 hrs | 229.8 PRU | Standard Deviation 24.6 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 3 hrs | 234.5 PRU | Standard Deviation 34.2 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 4 hrs | 215.5 PRU | Standard Deviation 67.4 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 5.5 hrs | NA PRU | — |
| Clopidogrel 1 Hr During Cangrelor | 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 | 2.5 hrs | 206.3 PRU | Standard Deviation 26.9 |
| Clopidogrel 1 Hr During Cangrelor | 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 | 5.5 hrs | NA PRU | — |
| Clopidogrel 1 Hr During Cangrelor | 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 | 4 hrs | 203.7 PRU | Standard Deviation 11.2 |
| Clopidogrel 1 Hr During Cangrelor | 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 | 2.25 hrs | 98.7 PRU | Standard Deviation 19.6 |
| Clopidogrel 1 Hr During Cangrelor | 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 | Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) | 197.3 PRU | Standard Deviation 15 |
| Clopidogrel 1 Hr During Cangrelor | 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 | 3 hrs | 212.7 PRU | Standard Deviation 10.3 |
| Clopidogrel 1 Hr During Cangrelor | 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 | 2.75 hrs | 214.3 PRU | Standard Deviation 11.9 |
Secondary
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
Population: Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel 30 Min After Cangrelor | 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 | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 208.0 PRU | Standard Deviation 30.2 |
| Prasugrel 30 Min After Cangrelor | 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 | 2 hrs | 5.3 PRU | Standard Deviation 2.1 |
| Prasugrel 30 Min After Cangrelor | 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 | 1.75 hrs | 3.3 PRU | Standard Deviation 2.3 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 7.3 PRU | Standard Deviation 5.1 |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 2 hrs | NA PRU | — |
| Clopidogrel Within 5 Min After Cangrelor | 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 | 1.75 hrs | 3.7 PRU | Standard Deviation 2.1 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 1.75 hrs | 25.0 PRU | Standard Deviation 30.5 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 17.7 PRU | Standard Deviation 18.2 |
| Clopidogrel 1.5 Hrs During Cangrelor | 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 | 2 hrs | 28.8 PRU | Standard Deviation 18.2 |
| Clopidogrel 1 Hr During Cangrelor | 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 | Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) | 7.0 PRU | Standard Deviation 2 |
| Clopidogrel 1 Hr During Cangrelor | 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 | 2 hrs | 5.7 PRU | Standard Deviation 2.1 |
| Clopidogrel 1 Hr During Cangrelor | 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 | 1.75 hrs | 6.3 PRU | Standard Deviation 1.5 |