Acute Coronary Syndromes
Conditions
Keywords
Acute Coronary Syndromes, Angina, Platelet Function, Coronary Angiography, Clinical Symptoms of Angina, Positive Stress Test
Brief summary
To investigate how platelets recover to normal function in subjects who have symptoms of a heart attack or unstable angina and who get a loading dose of prasugrel or clopidogrel for planned coronary angiography.
Interventions
DRUGprasugrel
taken orally, day one, single dose
DRUGclopidogrel
taken orally, day one, single dose
Sponsors
Daiichi Sankyo Co., Ltd.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Men or women ≥18 to \<80 years of age who present with any one of the following: * symptoms of Acute Coronary Syndromes (ACS) * clinical symptoms of angina, or a positive stress test or who return for routine follow up angiography post stent placement in whom co-administration of aspirin and a thienopyridine (that is, clopidogrel, ticlopidine, or prasugrel) is not contraindicated
Exclusion criteria
* Those presenting with ST-elevation MI (STEMI) * histories of refractory ventricular arrhythmias * an implanted defibrillator device * congestive heart failure (NYHA Class III or above) within 6 months prior to screening * significant hypertension * subjects with a history or clinical suspicion of cerebral vascular malformations, transient ischaemic attack, or stroke * bleeding disorders * women known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Returning to Baseline Platelet Function | Days 3, 5, 7, 9, and 11 | Participants were classified as having platelet function return to baseline after loading dose (LD) on the first day that P2Y12 Reaction Units (PRU) was no more than 60 PRU below baseline and remained in this range. PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Day When the Proportion of Participants Who Return to Baseline Platelet Function in the 30-mg and 60-mg Prasugrel Groups is Similar to the 600-mg Clopidogrel Group at Day 5 and Day 7 | Up through 11 days | The day at which the proportion of participants who return to baseline platelet P2Y12 receptor function in the prasugrel 30 mg and 60 mg LD groups is similar (within 10% absolute difference) to the proportion of subjects who return to baseline platelet P2Y12 receptor function at day 5 and day 7 in the clopidogrel 600 mg LD group, obtained from Kaplan Meier curves for the primary washout population, was to be presented. This outcome measure was not analyzed due to the limited sample size. |
| Number of Days to the Return of Baseline Platelet Function Following One Loading Dose (LD) | Up through 11 days | The return of baseline platelet function following one LD of prasugrel (30 mg or 60 mg) or 600 mg LD of clopidogrel assessed by Verify Now™ P2Y12 Reaction Units (VN-PRU). This outcome measure was not analyzed because it was not appropriate to estimate the days based on the non-inferiority approach due to the limited sample size. |
| Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU | Up through 11 days | To show effect of initial inhibition of platelet aggregation as measured by Accumetrics Verify Now™ P2Y12 on the day to return to baseline platelet function, a regression model was fitted with day to return as outcome variable and initial inhibition as fixed effect. Results are reported as the predicted day to return to baseline platelet function by derived VN-PRU percent (%) inhibition at 24 hours post LD. The derived VN-PRU % inhibition is calculated as a percent decrease of PRU from baseline using the following formula: (\[PRU at baseline - PRU at 24 hours post LD\]/PRU at baseline) x 100%. |
| Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by VN-PRU | Up through 11 days | PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation. This outcome measure was not analyzed due to the limited sample size. |
| Platelet Function 24 Hours Post Loading Dose | 24 hours post-loading dose | PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of ADP-stimulated platelet aggregation. |
| Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD | 24 hours post-loading dose | Platelet aggregation was assessed by Accumetrics Verify Now™ P2Y12, and poor responders were those with PRU greater than or equal to 230. |
| The Day on Which 50%, 75% and 90% of Subjects Return to Baseline Platelet Function Following a Single LD of 30-mg or 60-mg Prasugrel or 600-mg Clopidogrel | Up through 11 days | This outcome measure was not analyzed due to the limited sample size. |
| Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Up through 11 days | Return of baseline platelet function was assessed by Multiplate® ADP test and ADP test High Sensitivity (HS). Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. The agonist ADP was added to stirred whole blood after dilution (1:2 with 0.9% NaCl solution) in a final concentration of 6.4 µM (ADP Test) or in final concentration of 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADPtest HS). Platelet aggregation was continuously recorded for 5 minutes and quantified as area under the aggregation curve (AUC=AU\*min) of aggregation units (AU). |
| Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hours Post-LD) by LTA (5 and 20 μM ADP) | Up through 11 days | Maximum platelet aggregation (MPA) to 5 and 20 μM ADP were assessed by LTA. This outcome measure was not analyzed due to limited sample size. |
| Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Up through 11 days | The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADP test HS), area under the aggregation curve (AUC) was calculated. This outcome measure was not analyzed due to limited sample size. |
| Platelet Function by LTA at 5 and 20 μM ADP | 24 hours post-loading dose | MPA to 5 and 20 μM ADP were assessed by LTA. |
| Platelet Function by Multiplate® ADP Test and ADP Test HS | 24 hours post-loading dose | The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM PGE1 (ADP test HS), area under the aggregation curve (AUC) were calculated. |
| Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Up through 11 days | Initial inhibition of platelet aggregation was measured by LTA at 5 and 20 μM ADP. Maximum platelet aggregation (MPA) is reported by day. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clopidogrel 600 mg Clopidogrel 600 mg taken orally, day one, single dose (Loading Dose \[LD\]) | 10 |
| Prasugrel 60 mg Prasugrel 60 mg taken orally, day one, single dose (Loading Dose \[LD\]) | 10 |
| Prasugrel 30 mg Prasugrel 30 mg taken orally, day one, single dose (Loading Dose \[LD\]) | 9 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 5 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Clopidogrel 600 mg | Prasugrel 60 mg | Prasugrel 30 mg | Total |
|---|---|---|---|---|
| Age Continuous | 66.9 years STANDARD_DEVIATION 8.54 | 65.6 years STANDARD_DEVIATION 6.56 | 61.5 years STANDARD_DEVIATION 10.01 | 64.8 years STANDARD_DEVIATION 8.44 |
| Race/Ethnicity, Customized White | 10 participants | 10 participants | 9 participants | 29 participants |
| Region of Enrollment Germany | 10 participants | 10 participants | 9 participants | 29 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 7 Participants | 24 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 | 0 / 10 | 0 / 10 | 0 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 1 / 8 |
Outcome results
Primary
Percentage of Participants Returning to Baseline Platelet Function
Participants were classified as having platelet function return to baseline after loading dose (LD) on the first day that P2Y12 Reaction Units (PRU) was no more than 60 PRU below baseline and remained in this range. PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation.
Time frame: Days 3, 5, 7, 9, and 11
Population: Primary Washout Population: Included participants who completed the study, had evaluable pharmacodynamic (PD) data through Day 11. Participants with a missed visit were not included in the Primary Washout Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clopidogrel 600 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 11 | 100.0 percentage of participants |
| Clopidogrel 600 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 3 | 60.0 percentage of participants |
| Clopidogrel 600 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 7 | 100.0 percentage of participants |
| Clopidogrel 600 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 5 | 80.0 percentage of participants |
| Clopidogrel 600 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 9 | 100.0 percentage of participants |
| Prasugrel 60 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 5 | 10.0 percentage of participants |
| Prasugrel 60 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 11 | 100.0 percentage of participants |
| Prasugrel 60 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 9 | 100.0 percentage of participants |
| Prasugrel 60 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 3 | 0 percentage of participants |
| Prasugrel 60 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 7 | 60.0 percentage of participants |
| Prasugrel 30 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 11 | 100.0 percentage of participants |
| Prasugrel 30 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 3 | 0 percentage of participants |
| Prasugrel 30 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 5 | 0 percentage of participants |
| Prasugrel 30 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 9 | 100.0 percentage of participants |
| Prasugrel 30 mg | Percentage of Participants Returning to Baseline Platelet Function | Day 7 | 100.0 percentage of participants |
Secondary
Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU
To show effect of initial inhibition of platelet aggregation as measured by Accumetrics Verify Now™ P2Y12 on the day to return to baseline platelet function, a regression model was fitted with day to return as outcome variable and initial inhibition as fixed effect. Results are reported as the predicted day to return to baseline platelet function by derived VN-PRU percent (%) inhibition at 24 hours post LD. The derived VN-PRU % inhibition is calculated as a percent decrease of PRU from baseline using the following formula: (\[PRU at baseline - PRU at 24 hours post LD\]/PRU at baseline) x 100%.
Time frame: Up through 11 days
Population: ITT Washout Population: All randomized participants who received study drug LD, had an evaluable baseline PD measurement (pre-LD), and had at least 1 evaluable PD measurement post-LD. One participant discontinued on Day 3 without returning to baseline and is not included in analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clopidogrel 600 mg | Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU | 20% Initial Inhibition | 3.2 days |
| Clopidogrel 600 mg | Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU | 40% Initial Inhibition | 4.6 days |
| Clopidogrel 600 mg | Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU | 60% Initial Inhibition | 6.0 days |
| Clopidogrel 600 mg | Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU | 80% Initial Inhibition | 7.4 days |
p-value: <0.001Regression, Linear
Secondary
Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA)
Initial inhibition of platelet aggregation was measured by LTA at 5 and 20 μM ADP. Maximum platelet aggregation (MPA) is reported by day.
Time frame: Up through 11 days
Population: ITT Washout Population: All randomized participants who received the study drug LD, had an evaluable baseline PD measurement (pre-LD), and had at least 1 evaluable PD measurement post-LD.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 5 (5 μM ADP) (n=5, n=10, n=4) | 64.20 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 9 (20 μM ADP) (n=5, n=10, n=5) | 62.40 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 3 (20 μM ADP) (n=5, n=10, n=6) | 56.00 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 3 (5 μM ADP) (n=5, n=10, n=6) | 50.20 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 11 (20 μM ADP) (n=5, n=10, n=5) | 72.00 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 1 (20 μM ADP) (n=5, n=10, n=6) | 52.60 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 1 (5 μM ADP) (n=5, n=10, n=6) | 39.40 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Baseline (5 μM ADP) (n=5, n=10, n=6) | 64.40 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 7 (5 μM ADP) (n=5, n=10, n=5) | 60.40 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 5 (20 μM ADP) (n=5, n=10, n=4) | 70.40 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 11 (5 μM ADP) (n=5, n=10, n=5) | 61.80 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Baseline (20 μM ADP) (n=5, n=10, n=6) | 68.00 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 7 (20 μM ADP) (n=5, n=10, n=5) | 71.00 percent platelet aggregation |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 9 (5 μM ADP) (n=5, n=10, n=5) | 58.40 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 5 (5 μM ADP) (n=5, n=10, n=4) | 39.50 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Baseline (20 μM ADP) (n=5, n=10, n=6) | 72.70 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 1 (20 μM ADP) (n=5, n=10, n=6) | 27.30 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 3 (20 μM ADP) (n=5, n=10, n=6) | 42.50 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 5 (20 μM ADP) (n=5, n=10, n=4) | 47.00 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 7 (20 μM ADP) (n=5, n=10, n=5) | 58.30 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 9 (20 μM ADP) (n=5, n=10, n=5) | 62.00 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 11 (20 μM ADP) (n=5, n=10, n=5) | 65.20 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Baseline (5 μM ADP) (n=5, n=10, n=6) | 62.60 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 1 (5 μM ADP) (n=5, n=10, n=6) | 22.00 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 3 (5 μM ADP) (n=5, n=10, n=6) | 32.80 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 7 (5 μM ADP) (n=5, n=10, n=5) | 52.40 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 9 (5 μM ADP) (n=5, n=10, n=5) | 56.00 percent platelet aggregation |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 11 (5 μM ADP) (n=5, n=10, n=5) | 58.90 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 9 (5 μM ADP) (n=5, n=10, n=5) | 60.00 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 3 (5 μM ADP) (n=5, n=10, n=6) | 48.67 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 7 (20 μM ADP) (n=5, n=10, n=5) | 73.20 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 5 (20 μM ADP) (n=5, n=10, n=4) | 58.25 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 5 (5 μM ADP) (n=5, n=10, n=4) | 53.25 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 3 (20 μM ADP) (n=5, n=10, n=6) | 46.33 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Baseline (20 μM ADP) (n=5, n=10, n=6) | 76.33 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 7 (5 μM ADP) (n=5, n=10, n=5) | 65.40 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 1 (20 μM ADP) (n=5, n=10, n=6) | 31.67 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Baseline (5 μM ADP) (n=5, n=10, n=6) | 70.67 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 11 (20 μM ADP) (n=5, n=10, n=5) | 63.80 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 11 (5 μM ADP) (n=5, n=10, n=5) | 56.00 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 1 (5 μM ADP) (n=5, n=10, n=6) | 25.50 percent platelet aggregation |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) | Day 9 (20 μM ADP) (n=5, n=10, n=5) | 68.60 percent platelet aggregation |
Secondary
Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS)
Return of baseline platelet function was assessed by Multiplate® ADP test and ADP test High Sensitivity (HS). Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. The agonist ADP was added to stirred whole blood after dilution (1:2 with 0.9% NaCl solution) in a final concentration of 6.4 µM (ADP Test) or in final concentration of 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADPtest HS). Platelet aggregation was continuously recorded for 5 minutes and quantified as area under the aggregation curve (AUC=AU\*min) of aggregation units (AU).
Time frame: Up through 11 days
Population: ITT Washout Population: All randomized participants who received the study drug LD, had an evaluable baseline PD measurement (pre-LD), and had at least 1 evaluable PD measurement post-LD.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 5 (ADP HS) (n=5, n=10, n=4) | 256.80 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 9 (ADP) (n=5, n=10, n=5) | 529.40 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 3 (ADP) (n=5, n=10, n=6) | 347.60 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 3 (ADP HS) (n=5, n=10, n=6) | 257.60 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 11 (ADP) (n=5, n=10, n=5) | 555.00 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 1 (ADP) (n=5, n=10, n=6) | 248.80 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 1 (ADP HS) (n=5, n=10, n=6) | 166.80 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Baseline (ADP HS) (n=5, n=10, n=6) | 361.00 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 7 (ADP HS) (n=5, n=10, n=5) | 263.60 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 5 (ADP) (n=5, n=10, n=4) | 428.40 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 11 (ADP HS) (n=5, n=10, n=5) | 373.20 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Baseline (ADP) (n=5, n=10, n=6) | 536.60 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 7 (ADP) (n=5, n=10, n=5) | 478.80 Aggregation Units * minutes |
| Clopidogrel 600 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 9 (ADP HS) (n=5, n=10, n=5) | 388.20 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 5 (ADP HS) (n=5, n=10, n=4) | 114.10 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Baseline (ADP) (n=5, n=10, n=6) | 601.60 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 1 (ADP) (n=5, n=10, n=6) | 90.00 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 3 (ADP) (n=5, n=10, n=6) | 140.90 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 5 (ADP) (n=5, n=10, n=4) | 231.30 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 7 (ADP) (n=5, n=10, n=5) | 316.20 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 9 (ADP) (n=5, n=10, n=5) | 549.00 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 11 (ADP) (n=5, n=10, n=5) | 500.20 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Baseline (ADP HS) (n=5, n=10, n=6) | 411.70 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 1 (ADP HS) (n=5, n=10, n=6) | 34.50 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 3 (ADP HS) (n=5, n=10, n=6) | 79.30 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 7 (ADP HS) (n=5, n=10, n=5) | 189.50 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 9 (ADP HS) (n=5, n=10, n=5) | 344.60 Aggregation Units * minutes |
| Prasugrel 60 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 11 (ADP HS) (n=5, n=10, n=5) | 365.40 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 9 (ADP HS) (n=5, n=10, n=5) | 343.60 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 3 (ADP HS) (n=5, n=10, n=6) | 90.50 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 7 (ADP) (n=5, n=10, n=5) | 295.40 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 5 (ADP) (n=5, n=10, n=4) | 296.00 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 5 (ADP HS) (n=5, n=10, n=4) | 145.00 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 3 (ADP) (n=5, n=10, n=6) | 134.67 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Baseline (ADP) (n=5, n=10, n=6) | 459.33 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 7 (ADP HS) (n=5, n=10, n=5) | 170.60 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 1 (ADP) (n=5, n=10, n=6) | 118.17 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Baseline (ADP HS) (n=5, n=10, n=6) | 344.00 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 11 (ADP) (n=5, n=10, n=5) | 564.00 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 11 (ADP HS) (n=5, n=10, n=5) | 404.00 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 1 (ADP HS) (n=5, n=10, n=6) | 70.17 Aggregation Units * minutes |
| Prasugrel 30 mg | Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) | Day 9 (ADP) (n=5, n=10, n=5) | 484.40 Aggregation Units * minutes |
Secondary
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hours Post-LD) by LTA (5 and 20 μM ADP)
Maximum platelet aggregation (MPA) to 5 and 20 μM ADP were assessed by LTA. This outcome measure was not analyzed due to limited sample size.
Time frame: Up through 11 days
Population: Since this outcome measure was not analyzed due to the limited sample size, zero participants were included in the analysis.
Secondary
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by Multiplate® ADP Test and ADP Test High Sensitivity (HS)
The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADP test HS), area under the aggregation curve (AUC) was calculated. This outcome measure was not analyzed due to limited sample size.
Time frame: Up through 11 days
Population: Since this outcome measure was not analyzed due to the limited sample size, zero participants were included in the analysis.
Secondary
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by VN-PRU
PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation. This outcome measure was not analyzed due to the limited sample size.
Time frame: Up through 11 days
Population: Since this outcome measure was not analyzed due to the limited sample size, zero participants were included in the analysis.
Secondary
Number of Days to the Return of Baseline Platelet Function Following One Loading Dose (LD)
The return of baseline platelet function following one LD of prasugrel (30 mg or 60 mg) or 600 mg LD of clopidogrel assessed by Verify Now™ P2Y12 Reaction Units (VN-PRU). This outcome measure was not analyzed because it was not appropriate to estimate the days based on the non-inferiority approach due to the limited sample size.
Time frame: Up through 11 days
Population: Since this outcome measure was not analyzed due to the limited sample size, zero participants were included in the analysis.
Secondary
Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD
Platelet aggregation was assessed by Accumetrics Verify Now™ P2Y12, and poor responders were those with PRU greater than or equal to 230.
Time frame: 24 hours post-loading dose
Population: LD ITT Population: All randomized participants who received an LD with evaluable PD measurements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel 600 mg | Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD | 40.0 percentage of participants |
| Prasugrel 60 mg | Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD | 0 percentage of participants |
| Prasugrel 30 mg | Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD | 0 percentage of participants |
Secondary
Platelet Function 24 Hours Post Loading Dose
PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of ADP-stimulated platelet aggregation.
Time frame: 24 hours post-loading dose
Population: LD ITT population: All randomized participants who received an LD with evaluable PD measurements 24 hours post-LD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clopidogrel 600 mg | Platelet Function 24 Hours Post Loading Dose | 193.0 P2Y12 Reaction Units (PRU) | Standard Deviation 83.58 |
| Prasugrel 60 mg | Platelet Function 24 Hours Post Loading Dose | 32.5 P2Y12 Reaction Units (PRU) | Standard Deviation 20.79 |
| Prasugrel 30 mg | Platelet Function 24 Hours Post Loading Dose | 70.0 P2Y12 Reaction Units (PRU) | Standard Deviation 56.23 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.025ANCOVA
Secondary
Platelet Function by LTA at 5 and 20 μM ADP
MPA to 5 and 20 μM ADP were assessed by LTA.
Time frame: 24 hours post-loading dose
Population: LD ITT population: All randomized participants who received an LD with evaluable PD measurements 24 hours post-LD.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clopidogrel 600 mg | Platelet Function by LTA at 5 and 20 μM ADP | Maximum Aggregation (20 µM ADP) | 52.60 percent aggregation | Standard Deviation 20.6 |
| Clopidogrel 600 mg | Platelet Function by LTA at 5 and 20 μM ADP | Maximum Aggregation (5 µM ADP) | 39.40 percent aggregation | Standard Deviation 16.79 |
| Prasugrel 60 mg | Platelet Function by LTA at 5 and 20 μM ADP | Maximum Aggregation (20 µM ADP) | 27.30 percent aggregation | Standard Deviation 10.86 |
| Prasugrel 60 mg | Platelet Function by LTA at 5 and 20 μM ADP | Maximum Aggregation (5 µM ADP) | 22.00 percent aggregation | Standard Deviation 11.44 |
| Prasugrel 30 mg | Platelet Function by LTA at 5 and 20 μM ADP | Maximum Aggregation (20 µM ADP) | 31.67 percent aggregation | Standard Deviation 11.13 |
| Prasugrel 30 mg | Platelet Function by LTA at 5 and 20 μM ADP | Maximum Aggregation (5 µM ADP) | 25.50 percent aggregation | Standard Deviation 8.89 |
Secondary
Platelet Function by Multiplate® ADP Test and ADP Test HS
The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM PGE1 (ADP test HS), area under the aggregation curve (AUC) were calculated.
Time frame: 24 hours post-loading dose
Population: LD ITT Population: All randomized participants who received an LD with evaluable PD measurements 24 hours post-LD.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clopidogrel 600 mg | Platelet Function by Multiplate® ADP Test and ADP Test HS | ADP Test HS AUC | 166.80 aggregation units*minute | Standard Deviation 82.24 |
| Clopidogrel 600 mg | Platelet Function by Multiplate® ADP Test and ADP Test HS | ADP Test AUC | 248.80 aggregation units*minute | Standard Deviation 120.54 |
| Prasugrel 60 mg | Platelet Function by Multiplate® ADP Test and ADP Test HS | ADP Test HS AUC | 34.50 aggregation units*minute | Standard Deviation 28.33 |
| Prasugrel 60 mg | Platelet Function by Multiplate® ADP Test and ADP Test HS | ADP Test AUC | 90.00 aggregation units*minute | Standard Deviation 27.46 |
| Prasugrel 30 mg | Platelet Function by Multiplate® ADP Test and ADP Test HS | ADP Test AUC | 118.17 aggregation units*minute | Standard Deviation 46.61 |
| Prasugrel 30 mg | Platelet Function by Multiplate® ADP Test and ADP Test HS | ADP Test HS AUC | 70.17 aggregation units*minute | Standard Deviation 36.02 |
Secondary
The Day on Which 50%, 75% and 90% of Subjects Return to Baseline Platelet Function Following a Single LD of 30-mg or 60-mg Prasugrel or 600-mg Clopidogrel
This outcome measure was not analyzed due to the limited sample size.
Time frame: Up through 11 days
Population: Since this outcome measure was not analyzed due to the limited sample size, zero participants were included in the analysis.
Secondary
The Day When the Proportion of Participants Who Return to Baseline Platelet Function in the 30-mg and 60-mg Prasugrel Groups is Similar to the 600-mg Clopidogrel Group at Day 5 and Day 7
The day at which the proportion of participants who return to baseline platelet P2Y12 receptor function in the prasugrel 30 mg and 60 mg LD groups is similar (within 10% absolute difference) to the proportion of subjects who return to baseline platelet P2Y12 receptor function at day 5 and day 7 in the clopidogrel 600 mg LD group, obtained from Kaplan Meier curves for the primary washout population, was to be presented. This outcome measure was not analyzed due to the limited sample size.
Time frame: Up through 11 days
Population: Since this outcome measure was not analyzed due to the limited sample size, zero participants were included in the analysis.