Coronary Arteriosclerosis, Acute Coronary Syndrome
Conditions
Brief summary
This study will compare the effect of a prasugrel 10-mg maintenance dose with a clopidogrel 75-mg maintenance dose on platelet activity, approximately 1 week after the first dose of study drug, in subjects who have been taking clopidogrel 75 mg daily following a percutaneous coronary intervention (PCI) with placement of a stent, performed to treat acute coronary syndrome (ACS).
Interventions
DRUGprasugrel 60 mg
60 mg (six 10-mg tablets) taken orally
oral, as blinding mechanism
DRUGprasugrel 10 mg
10 mg tablet taken orally
DRUGclopidogrel
75 mg tablet taken orally
DRUGprasugrel placebo
oral, as blinding mechanism.
Sponsors
Daiichi Sankyo
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Present with a recent history of an ACS event based on the disease diagnostic criteria between 30 and 330 days prior to enrollment, and who state that they are supposed to be taking daily aspirin and maintenance dose 75-mg clopidogrel. * Are of a legal age (and at least 18 years of age but less than 75 years of age) and competent mental condition to provide written informed consent before entering the study.
Exclusion criteria
* Left main coronary artery stent or left anterior descending (LAD) bifurcation stent. * Have any form of coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\]) planned to occur during the study (from signing consent through the final visit). * Have undergone CABG or PCI within 30 days of entry into the study. * Receiving or will receive oral anticoagulation or other antiplatelet therapy (other than aspirin and clopidogrel) that cannot be safely discontinued for the duration of the study. * Receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) that cannot be discontinued or are anticipated to require daily treatment with NSAIDs during the study. * Have any of the following: history of ischemic or hemorrhagic stroke intracranial neoplasm, arteriovenous malformation, or aneurysm history of transient ischemic attack (TIA), have a body weight less than 60 kilograms (kg).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Platelet Aggregation (MPA) to 20 Micromolar (uM) Adenosine Diphosphase (ADP) | 1 week after first dose of randomized study drug | Maximum platelet aggregation (MPA) to 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 hours, 24 hours, 1 week, 2 weeks after first dose of randomized study drug | Maximum platelet aggregation (MPA) to 5 and 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA). |
| Maximum Platelet Aggregation (MPA) to 20 uM ADP According to Clopidogrel Use at Time of Qualifying Acute Coronary Syndrome (ACS) Event | End of 14 day open label | Data provided are the MPA to 20 micromolar ADP while taking clopidogrel (measurement taken at end of the 14 day open label phase) grouped by subjects who were taking clopidogrel at the time of the qualifying ACS event compared with subjects who were not taking clopidogrel at the time of the qualifying ACS event. |
| Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 hours, 24 hours, 1 week, 2 weeks after first dose of randomized study drug | Residual platelet aggregation after the addition 5 and 20 micromolar ADP as measured with light transmittance aggregometry (LTA). |
| Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | 1 week after randomized study drug | Correlation Coefficient comparing the Accumetrics VerifyNow™ P2Y12 device with light transmittance aggregometry (LTA) for monitoring platelet aggregation. |
| Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | End of 14 day open label (baseline); 24 Hours, 7 days, 14 days after first dose of randomized drug | Bleeding events were classified as Major Bleeding, Minor Bleeding, or Insignificant according to TIMI criteria. Major Bleeding: any intracranial hemorrhage OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 gm/dL from baseline. Minor Bleeding: any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in Hgb of ≥3 gm/dL but \<5 gm/dL from baseline. Insignificant Bleeding: any bleeding event that does not meet criteria for a Major or Minor Bleed. |
Countries
United States
Participant flow
Pre-assignment details
30-330 days after acute coronary syndrome event, patients participated in 2 week open-label clopidogrel phase. Patients were then randomized to either 22-26 hour loading doses of: 60-mg prasugrel, 10-mg prasugrel, or 75-mg clopidogrel, then continued 2-week maintenance phase of 10-mg prasugrel, 10-mg prasugrel, or 75-mg clopidogrel, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel 10/10 mg Open label dose of clopidogrel 75 milligram (mg) for 10 to 14 days. Upon completion, randomization to a single loading dose of prasugrel 10 mg and placebo, followed by maintenance dose of prasugrel 10 mg taken for 13 to 15 days. | 47 |
| Clopidogrel 75/75 mg Open label dose of clopidogrel 75 mg for 10 to 14 days. Upon completion, randomization to a single loading dose of clopidogrel 75 mg and placebo, followed by maintenance dose of clopidogrel 75 mg taken for 13 to 15 days. | 48 |
| Prasugrel 60/10 mg Open label dose of clopidogrel 75 mg for 10 to 14 days. Upon completion, randomized to a single loading dose of prasugrel 60 mg and placebo followed by maintenance dose of prasugrel 10 mg taken for 13 to 15 days. | 44 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Subject non-compliance | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | Prasugrel 10/10 mg | Clopidogrel 75/75 mg | Prasugrel 60/10 mg | Total |
|---|---|---|---|---|
| Age Continuous | 57.6 years STANDARD_DEVIATION 8.18 | 56.9 years STANDARD_DEVIATION 8.93 | 58.7 years STANDARD_DEVIATION 9.16 | 57.7 years STANDARD_DEVIATION 8.73 |
| Race/Ethnicity, Customized African | 7 participants | 13 participants | 6 participants | 26 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian | 39 participants | 30 participants | 37 participants | 106 participants |
| Race/Ethnicity, Customized Other | 1 participants | 5 participants | 1 participants | 7 participants |
| Region of Enrollment United States | 47 participants | 48 participants | 44 participants | 139 participants |
| Sex: Female, Male Female | 12 Participants | 18 Participants | 15 Participants | 45 Participants |
| Sex: Female, Male Male | 35 Participants | 30 Participants | 29 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 47 | 25 / 48 | 11 / 44 |
| serious Total, serious adverse events | 3 / 47 | 0 / 48 | 0 / 44 |
Outcome results
Primary
Maximum Platelet Aggregation (MPA) to 20 Micromolar (uM) Adenosine Diphosphase (ADP)
Maximum platelet aggregation (MPA) to 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA).
Time frame: 1 week after first dose of randomized study drug
Population: The primary analysis population was the pharmacodynamic (PD) population which included all randomized participants who had blood draws for MPA at 1 week after randomization who met compliance criteria, and who had last dose of study drug the day prior to the blood draw for MPA.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) to 20 Micromolar (uM) Adenosine Diphosphase (ADP) | 41.1 percent maximum platelet aggregation (%) | Standard Error 1.99 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) to 20 Micromolar (uM) Adenosine Diphosphase (ADP) | 55.0 percent maximum platelet aggregation (%) | Standard Error 2.09 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) to 20 Micromolar (uM) Adenosine Diphosphase (ADP) | 41.0 percent maximum platelet aggregation (%) | Standard Error 2 |
p-value: <0.000195% CI: [-19.1, -8.73]ANOVA
p-value: <0.000195% CI: [-19.26, -8.71]ANCOVA
Secondary
Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week
Correlation Coefficient comparing the Accumetrics VerifyNow™ P2Y12 device with light transmittance aggregometry (LTA) for monitoring platelet aggregation.
Time frame: 1 week after randomized study drug
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for MPA, who met compliance criteria, and who had last dose of study drug the day prior to the blood draw for MPA.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel 10/10 mg | Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | MPA (20 uM ADP) at 1 week | 0.564 correlation coefficient |
| Prasugrel 10/10 mg | Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | RPA (20 uM ADP) at 1 week | 0.640 correlation coefficient |
| Clopidogrel 75/75 mg | Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | MPA (20 uM ADP) at 1 week | 0.426 correlation coefficient |
| Clopidogrel 75/75 mg | Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | RPA (20 uM ADP) at 1 week | 0.425 correlation coefficient |
| Prasugrel 60/10 mg | Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | MPA (20 uM ADP) at 1 week | 0.439 correlation coefficient |
| Prasugrel 60/10 mg | Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | RPA (20 uM ADP) at 1 week | 0.547 correlation coefficient |
p-value: 0.0005Pearson Correlation Coefficient
p-value: <0.0001Pearson Correlation Coefficient
p-value: 0.015Pearson Correlation Coefficient
p-value: 0.0152Pearson Correlation Coefficient
p-value: 0.0153Pearson Correlation Coefficient
p-value: 0.0018Pearson Correlation Coefficient
Secondary
Maximum Platelet Aggregation (MPA) to 20 uM ADP According to Clopidogrel Use at Time of Qualifying Acute Coronary Syndrome (ACS) Event
Data provided are the MPA to 20 micromolar ADP while taking clopidogrel (measurement taken at end of the 14 day open label phase) grouped by subjects who were taking clopidogrel at the time of the qualifying ACS event compared with subjects who were not taking clopidogrel at the time of the qualifying ACS event.
Time frame: End of 14 day open label
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for MPA, who met compliance criteria, and who had last dose of study drug the day prior to the blood draw for MPA. Grouped according to clopidogrel use at time of ACS event and no clopidogrel use at time of ACS event.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) to 20 uM ADP According to Clopidogrel Use at Time of Qualifying Acute Coronary Syndrome (ACS) Event | 60.73 percent maximum platelet aggregation (%) | Standard Deviation 18.729 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) to 20 uM ADP According to Clopidogrel Use at Time of Qualifying Acute Coronary Syndrome (ACS) Event | 55.53 percent maximum platelet aggregation (%) | Standard Deviation 14.356 |
Comparison: The mean of MPA 20 uM ADP at the end of Clopidogrel open label of patients on chronic clopidogrel at the time of qualifying events was compared to the mean MPA of patients not using clopidogrel at this time.p-value: 0.1824t-test, 2 sided
Comparison: The variance of MPA 20 uM ADP at the end of Clopidogrel open label of patients on chronic clopidogrel at the time of qualifying events was compared to the variance of MPA for patients not using clopidogrel at this time.p-value: 0.1101F-test
Secondary
Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks
Maximum platelet aggregation (MPA) to 5 and 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA).
Time frame: 2 hours, 24 hours, 1 week, 2 weeks after first dose of randomized study drug
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for MPA, who met compliance criteria, and who had last dose of study drug the day prior to the blood draw for MPA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (20 uM ADP) | 49.46 percent maximum platelet aggregation (%) | Standard Deviation 21.243 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (20 uM ADP) | 52.29 percent maximum platelet aggregation (%) | Standard Deviation 16.511 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (20 uM ADP) | 42.95 percent maximum platelet aggregation (%) | Standard Deviation 14.963 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (20 uM ADP) | 40.84 percent maximum platelet aggregation (%) | Standard Deviation 13.359 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (5 uM ADP) | 37.87 percent maximum platelet aggregation (%) | Standard Deviation 16.547 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (5 uM ADP) | 38.84 percent maximum platelet aggregation (%) | Standard Deviation 14.841 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (5 uM ADP) | 32.44 percent maximum platelet aggregation (%) | Standard Deviation 11.739 |
| Prasugrel 10/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (5 uM ADP) | 30.18 percent maximum platelet aggregation (%) | Standard Deviation 11.444 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (20 uM ADP) | 53.80 percent maximum platelet aggregation (%) | Standard Deviation 14.878 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (5 uM ADP) | 41.94 percent maximum platelet aggregation (%) | Standard Deviation 14.436 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (20 uM ADP) | 52.25 percent maximum platelet aggregation (%) | Standard Deviation 16.856 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (5 uM ADP) | 37.25 percent maximum platelet aggregation (%) | Standard Deviation 12.579 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (5 uM ADP) | 40.88 percent maximum platelet aggregation (%) | Standard Deviation 14.54 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (20 uM ADP) | 48.07 percent maximum platelet aggregation (%) | Standard Deviation 17.728 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (20 uM ADP) | 53.80 percent maximum platelet aggregation (%) | Standard Deviation 14.504 |
| Clopidogrel 75/75 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (5 uM ADP) | 41.05 percent maximum platelet aggregation (%) | Standard Deviation 13.57 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (20 uM ADP) | 40.64 percent maximum platelet aggregation (%) | Standard Deviation 10.182 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (20 uM ADP) | 27.36 percent maximum platelet aggregation (%) | Standard Deviation 10.812 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (20 uM ADP) | 26.65 percent maximum platelet aggregation (%) | Standard Deviation 10.875 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (20 uM ADP) | 38.61 percent maximum platelet aggregation (%) | Standard Deviation 13.373 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (5 uM ADP) | 31.45 percent maximum platelet aggregation (%) | Standard Deviation 11.446 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (5 uM ADP) | 20.94 percent maximum platelet aggregation (%) | Standard Deviation 11.476 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (5 uM ADP) | 19.97 percent maximum platelet aggregation (%) | Standard Deviation 11.263 |
| Prasugrel 60/10 mg | Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (5 uM ADP) | 28.64 percent maximum platelet aggregation (%) | Standard Deviation 13.534 |
p-value: 0.405595% CI: [-8.22, 3.35]Repeated Measures Analysis
p-value: <0.000195% CI: [-29.3, -17.51]Repeated Measures Analysis
p-value: 0.06895% CI: [-8.82, 0.32]Repeated Measures Analysis
Comparison: Comparison of MPA to 20 uM ADP at 24 hoursp-value: <0.000195% CI: [-33.2, -23.94]Repeated Measures Analysis
p-value: <0.000195% CI: [-19.96, -9.65]Repeated Measures Analysis
p-value: <0.000195% CI: [-19.87, -9.32]Repeated Measures Analysis
p-value: <0.000195% CI: [-20.3, -9.22]Repeated Measures Analysis
p-value: <0.000195% CI: [-20.59, -9.22]Repeated Measures Analysis
p-value: 0.550195% CI: [-5.85, 3.14]Repeated Measures Analysis
p-value: <0.000195% CI: [-21.55, -12.37]Repeated Measures Analysis
p-value: 0.075295% CI: [-8.58, 0.42]Repeated Measures Analysis
p-value: <0.000195% CI: [-24.81, -15.64]Repeated Measures Analysis
p-value: <0.000195% CI: [-17.21, -7.5]Repeated Measures Analysis
p-value: <0.000195% CI: [-15.79, -5.79]Repeated Measures Analysis
p-value: <0.000195% CI: [-17.41, -7.72]Repeated Measures Analysis
p-value: <0.000195% CI: [-16.8, -6.82]Repeated Measures Analysis
Secondary
Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria
Bleeding events were classified as Major Bleeding, Minor Bleeding, or Insignificant according to TIMI criteria. Major Bleeding: any intracranial hemorrhage OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 gm/dL from baseline. Minor Bleeding: any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in Hgb of ≥3 gm/dL but \<5 gm/dL from baseline. Insignificant Bleeding: any bleeding event that does not meet criteria for a Major or Minor Bleed.
Time frame: End of 14 day open label (baseline); 24 Hours, 7 days, 14 days after first dose of randomized drug
Population: Safety Population - all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Minor Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Insignificant Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Any Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Any Bleeding at Any Time During Randomized Period | 4 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Minor Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Insignificant Bleeding | 2 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Insignificant Bleeding | 2 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Major Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Minor Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Any Bleeding | 2 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Major Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Any Bleeding | 2 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Major Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Minor Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Major Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Any Bleeding | 0 Participants |
| Prasugrel 10/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Insignificant Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Insignificant Bleeding | 2 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Any Bleeding at Any Time During Randomized Period | 6 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Any Bleeding | 3 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Insignificant Bleeding | 3 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Minor Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Major Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Any Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Insignificant Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Minor Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Major Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Any Bleeding | 2 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Minor Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Major Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Any Bleeding | 4 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Insignificant Bleeding | 4 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Minor Bleeding | 0 Participants |
| Clopidogrel 75/75 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Major Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Any Bleeding | 1 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Minor Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Major Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Major Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Major Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Minor Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Minor Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Any Bleeding | 2 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Baseline: Insignificant Bleeding | 1 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Any Bleeding at Any Time During Randomized Period | 6 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Major Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 14: Insignificant Bleeding | 2 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Any Bleeding | 3 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Minor Bleeding | 0 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Insignificant Bleeding | 1 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Day 7: Insignificant Bleeding | 3 Participants |
| Prasugrel 60/10 mg | Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Hour 24: Any Bleeding | 1 Participants |
Secondary
Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks
Residual platelet aggregation after the addition 5 and 20 micromolar ADP as measured with light transmittance aggregometry (LTA).
Time frame: 2 hours, 24 hours, 1 week, 2 weeks after first dose of randomized study drug
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for MPA, who met compliance criteria, and who had last dose of study drug the day prior to the blood draw for MPA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (20 uM ADP) | 32.06 percent residual platelet aggregation | Standard Deviation 24.462 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (20 uM ADP) | 32.97 percent residual platelet aggregation | Standard Deviation 21.858 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (20 uM ADP) | 22.92 percent residual platelet aggregation | Standard Deviation 17.961 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (20 uM ADP) | 18.89 percent residual platelet aggregation | Standard Deviation 14.401 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (5 uM ADP) | 18.83 percent residual platelet aggregation | Standard Deviation 17.574 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (5 uM ADP) | 19.18 percent residual platelet aggregation | Standard Deviation 16.448 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (5 uM ADP) | 11.11 percent residual platelet aggregation | Standard Deviation 10.325 |
| Prasugrel 10/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (5 uM ADP) | 10.03 percent residual platelet aggregation | Standard Deviation 9.247 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (20 uM ADP) | 34.45 percent residual platelet aggregation | Standard Deviation 21.752 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (5 uM ADP) | 21.57 percent residual platelet aggregation | Standard Deviation 18.829 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (20 uM ADP) | 34.56 percent residual platelet aggregation | Standard Deviation 19.515 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (5 uM ADP) | 14.84 percent residual platelet aggregation | Standard Deviation 12.767 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (5 uM ADP) | 19.28 percent residual platelet aggregation | Standard Deviation 14.824 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (5 uM ADP) | 19.66 percent residual platelet aggregation | Standard Deviation 14.672 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (20 uM ADP) | 28.21 percent residual platelet aggregation | Standard Deviation 21.792 |
| Clopidogrel 75/75 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (20 uM ADP) | 35.16 percent residual platelet aggregation | Standard Deviation 19.379 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (20 uM ADP) | 4.70 percent residual platelet aggregation | Standard Deviation 5.688 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (5 uM ADP) | 9.43 percent residual platelet aggregation | Standard Deviation 8.621 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (20 uM ADP) | 5.10 percent residual platelet aggregation | Standard Deviation 7.814 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Week (20 uM ADP) | 15.17 percent residual platelet aggregation | Standard Deviation 15.127 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (5 uM ADP) | 9.94 percent residual platelet aggregation | Standard Deviation 10.37 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 24 Hour (5 uM ADP) | 4.45 percent residual platelet aggregation | Standard Deviation 4.545 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 2 Hour (5 uM ADP) | 4.17 percent residual platelet aggregation | Standard Deviation 4.878 |
| Prasugrel 60/10 mg | Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | 1 Week (20 uM ADP) | 17.94 percent residual platelet aggregation | Standard Deviation 12.961 |
p-value: 0.346695% CI: [-9.5, 3.37]Repeated Measures Analysis
p-value: <0.000195% CI: [-33.4, -20.33]Repeated Measures Analysis
p-value: 0.012795% CI: [-13.04, -1.6]Repeated Measures Analysis
p-value: <0.000195% CI: [-39.99, -28.42]Repeated Measures Analysis
p-value: <0.000195% CI: [-25.58, -11.09]Repeated Measures Analysis
p-value: <0.000195% CI: [-27.09, -12.26]Repeated Measures Analysis
p-value: <0.000195% CI: [-28.42, -14.77]Repeated Measures Analysis
p-value: <0.000195% CI: [-29.61, -15.63]Repeated Measures Analysis
p-value: 0.495495% CI: [-3.11, 6.38]Repeated Measures Analysis
p-value: <0.000195% CI: [-15.92, -6.24]Repeated Measures Analysis
p-value: 0.197195% CI: [-8.31, 1.74]Repeated Measures Analysis
p-value: <0.000195% CI: [-20.98, -10.75]Repeated Measures Analysis
p-value: <0.000195% CI: [-18.81, -7.32]Repeated Measures Analysis
p-value: 0.000195% CI: [-17.91, -6.09]Repeated Measures Analysis
p-value: <0.000195% CI: [-15.64, -6.32]Repeated Measures Analysis
p-value: <0.000195% CI: [-14.67, -5.09]Repeated Measures Analysis