Coronary Artery Disease
Conditions
Keywords
Platelet function
Brief summary
The 5-milligram (mg) maintenance dose (MD) of prasugrel in very elderly patients with coronary artery disease produces a pharmacodynamic response within the same therapeutic range as 10-mg MD in non-elderly patients.
Interventions
DRUGprasugrel
administered orally, daily for 12 days
DRUGclopidogrel
Administered orally, daily for 12 days
Sponsors
Daiichi Sankyo Co., Ltd.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants (Either: at least 45 years of age, but less than 65 years of age OR 75 years of age or older) with a history of stable coronary artery disease who are not currently indicated for treatment with a thienopyridine (that is, prasugrel, clopidogrel, or ticlopidine) * Provision of written informed consent * Body weight greater than or equal to 60 kilograms (kg) * For women of child-bearing potential only (that is, women who are not surgically or chemically sterilised and who are between menarche and 1 year post menopause), test negative for pregnancy (based on a urine or serum pregnancy test to be performed before randomisation) and agree to use a reliable method of birth control during the study
Exclusion criteria
* Unstable coronary artery disease * Myocardial Infarction (MI) within the previous 30 days * Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft Surgery (CABG) within the previous 90 days * History of refractory ventricular arrhythmias within the last 6 months; an implanted defibrillator device; congestive heart failure within 6 months prior to screening; major surgery, or severe trauma, fracture or organ biopsy within 3 months prior to enrollment * Any planned surgical procedure or any coronary revascularisation (surgical or percutaneous) planned within 60 days following randomisation * Any known contraindication to treatment with an antiplatelet agent * Significant hypertension at the time of screening or randomisation * Clinically significant out-of-range values for platelet count or haemoglobin at screening, in the investigator's opinion, or results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the study population, as determined by the investigator * Prior history or presence of significant bleeding disorders, abnormal bleeding tendency, or personal history of coagulation or bleeding disorders * Prior history or clinical suspicion of cerebral vascular malformations, intracranial neoplasm, Transient Ischemic Attack (TIA) or stroke * Prior history of thrombocytopenia or thrombocytosis * Use of antiplatelet agents (besides aspirin) within 10 days prior to screening; the use (or planned use) of heparin, oral anticoagulants, or fibrinolytic agents within 30 days of screening; or participants receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period | Baseline, 12 days | Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). Lower MPA values reflect stronger platelet inhibition, whereas higher MPA values reflect weaker inhibition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline, Day 12 | Vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12, whereas a higher PRI reflects weaker inhibition of P2Y12. |
| Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline, Day 12 | The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in P2Y12 reaction units (PRU). PRU report the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of the rate and extent of platelet aggregation in the presence of adenosine phosphate ADP. A lower PRU reflects stronger inhibition of P2Y12, whereas a higher PRU reflects weaker inhibition of P2Y12. |
| Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | Baseline up to 4 hours post-dose | A descriptive pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing prasugrel and clopidogrel active metabolite exposures to MPA in response to 20 µM ADP (by LTA) was conducted as originally intended; however, the graphic output from that analysis is not possible here. Therefore, the PK portion is presented here as AUC and the PD portion is presented in Secondary Outcome Measure #5. AUC was calculated through the last scheduled sampling time of 4 hours \[AUC (0-4)\] or through the sampling time of the last quantifiable concentration prior to 4 hours. AUC values were denoted AUC(0-tlast) in both instances. |
| Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline, Day 12 | Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition. |
Countries
Ireland, Netherlands, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Very Elderly, Drug Sequence ABC Participants (≥75 years of age) in this arm received study drug sequence ABC. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg. | 36 |
| Very Elderly; Drug Sequence ACB Participants (≥75 years of age) in this arm received study drug sequence ACB. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg. | 37 |
| Non-Elderly; Drug Sequence BAC Participants (≥45 to \<65 years of age) in this arm received study drug sequence BAC. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg. | 42 |
| Non-Elderly; Drug Sequence BCA Participants (≥45 to \<65 years of age) in this arm received study drug sequence BCA. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg. | 40 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 |
| Period 1 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 3 | Adverse Event | 0 | 1 | 1 | 0 | 0 | 0 |
| Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Very Elderly, Drug Sequence ABC | Very Elderly; Drug Sequence ACB | Non-Elderly; Drug Sequence BAC | Non-Elderly; Drug Sequence BCA | Total |
|---|---|---|---|---|---|
| Age Continuous | 79.02 years STANDARD_DEVIATION 2.87 | 78.74 years STANDARD_DEVIATION 3.12 | 57.11 years STANDARD_DEVIATION 4.75 | 55.46 years STANDARD_DEVIATION 5.53 | 66.94 years STANDARD_DEVIATION 12.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 9 Participants | 14 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 28 Participants | 30 Participants | 32 Participants | 26 Participants | 116 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 34 Participants | 40 Participants | 32 Participants | 141 Participants |
| Region of Enrollment Ireland | 3 participants | 3 participants | 7 participants | 6 participants | 19 participants |
| Region of Enrollment Netherlands | 3 participants | 4 participants | 2 participants | 1 participants | 10 participants |
| Region of Enrollment Sweden | 22 participants | 23 participants | 23 participants | 19 participants | 87 participants |
| Region of Enrollment United States | 8 participants | 7 participants | 10 participants | 14 participants | 39 participants |
| Sex: Female, Male Female | 8 Participants | 11 Participants | 7 Participants | 10 Participants | 36 Participants |
| Sex: Female, Male Male | 28 Participants | 26 Participants | 35 Participants | 30 Participants | 119 Participants |
| Tobacco Use Status at Baseline No | 32 participants | 36 participants | 29 participants | 29 participants | 126 participants |
| Tobacco Use Status at Baseline Yes | 4 participants | 1 participants | 13 participants | 11 participants | 29 participants |
| Weight | 88.49 kilograms (kg) STANDARD_DEVIATION 10.92 | 82.30 kilograms (kg) STANDARD_DEVIATION 10.74 | 92.85 kilograms (kg) STANDARD_DEVIATION 20.01 | 93.36 kilograms (kg) STANDARD_DEVIATION 17.32 | 89.45 kilograms (kg) STANDARD_DEVIATION 16.01 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 73 | 31 / 71 | 25 / 72 | 23 / 79 | 39 / 82 | 23 / 79 |
| serious Total, serious adverse events | 0 / 73 | 2 / 71 | 2 / 72 | 0 / 79 | 2 / 82 | 0 / 79 |
Outcome results
Primary
Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period
Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). Lower MPA values reflect stronger platelet inhibition, whereas higher MPA values reflect weaker inhibition.
Time frame: Baseline, 12 days
Population: All randomized participants who continued in the study through the Day 12 visit, and who had at least 1 evaluable PD assessment at the Day 12 visit. Participants were analysed based on randomized treatment assignment, regardless of the study drug they took.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 5 mg Prasugrel (Elderly) | Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period | Baseline | 78.00 percentage of aggregation |
| 5 mg Prasugrel (Elderly) | Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period | Period 1 (12 days) (n=71, 79) | 58.00 percentage of aggregation |
| 10 mg Prasugrel (Non-Elderly) | Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period | Baseline | 75.00 percentage of aggregation |
| 10 mg Prasugrel (Non-Elderly) | Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period | Period 1 (12 days) (n=71, 79) | 46.00 percentage of aggregation |
95% CI: [1, 9]
Secondary
Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing
A descriptive pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing prasugrel and clopidogrel active metabolite exposures to MPA in response to 20 µM ADP (by LTA) was conducted as originally intended; however, the graphic output from that analysis is not possible here. Therefore, the PK portion is presented here as AUC and the PD portion is presented in Secondary Outcome Measure #5. AUC was calculated through the last scheduled sampling time of 4 hours \[AUC (0-4)\] or through the sampling time of the last quantifiable concentration prior to 4 hours. AUC values were denoted AUC(0-tlast) in both instances.
Time frame: Baseline up to 4 hours post-dose
Population: All available PK sample data from all treated participants who contributed complete PK profiles.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Prasugrel (Elderly) | Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | 18.9 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| 10 mg Prasugrel (Non-Elderly) | Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | 41.2 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| 75 mg Clopidogrel (Elderly) | Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | 13.0 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 62 |
| 5 mg Prasugrel (Non-Elderly) | Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | 16.1 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| 10 mg Prasugrel (Non-Elderly) | Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | 36.7 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
| 75 mg Clopidogrel (Non-Elderly) | Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing | 11.8 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 68 |
Secondary
Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy
Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.
Time frame: Baseline, Day 12
Population: All randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable pharmacodynamic (PD) measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Prasugrel (Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline | 79.10 percentage of aggregation | Standard Deviation 9.73 |
| 5 mg Prasugrel (Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Day 12 (n=71, 70, 70, 78, 79, 79) | 57.05 percentage of aggregation | Standard Deviation 13.98 |
| 10 mg Prasugrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline | 78.75 percentage of aggregation | Standard Deviation 9.53 |
| 10 mg Prasugrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Day 12 (n=71, 70, 70, 78, 79, 79) | 45.54 percentage of aggregation | Standard Deviation 11.07 |
| 75 mg Clopidogrel (Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline | 79.11 percentage of aggregation | Standard Deviation 9.8 |
| 75 mg Clopidogrel (Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Day 12 (n=71, 70, 70, 78, 79, 79) | 63.08 percentage of aggregation | Standard Deviation 13.73 |
| 5 mg Prasugrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline | 76.61 percentage of aggregation | Standard Deviation 8.07 |
| 5 mg Prasugrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Day 12 (n=71, 70, 70, 78, 79, 79) | 56.83 percentage of aggregation | Standard Deviation 11.62 |
| 10 mg Prasugrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline | 76.61 percentage of aggregation | Standard Deviation 8.02 |
| 10 mg Prasugrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Day 12 (n=71, 70, 70, 78, 79, 79) | 45.83 percentage of aggregation | Standard Deviation 11.82 |
| 75 mg Clopidogrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Baseline | 76.61 percentage of aggregation | Standard Deviation 8.02 |
| 75 mg Clopidogrel (Non-Elderly) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy | Day 12 (n=71, 70, 70, 78, 79, 79) | 59.09 percentage of aggregation | Standard Deviation 13.44 |
Secondary
Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy
Vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12, whereas a higher PRI reflects weaker inhibition of P2Y12.
Time frame: Baseline, Day 12
Population: All randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable pharmacodynamic (PD) measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Prasugrel (Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Day 12 (n=67, 65, 67, 73, 74, 73) | 44.30 percentage platelet reactive index (PRI) | Standard Deviation 18.87 |
| 5 mg Prasugrel (Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline (n=68, 66, 67, 71, 72, 72) | 85.62 percentage platelet reactive index (PRI) | Standard Deviation 4.28 |
| 10 mg Prasugrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline (n=68, 66, 67, 71, 72, 72) | 85.66 percentage platelet reactive index (PRI) | Standard Deviation 4.32 |
| 10 mg Prasugrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Day 12 (n=67, 65, 67, 73, 74, 73) | 22.66 percentage platelet reactive index (PRI) | Standard Deviation 11.9 |
| 75 mg Clopidogrel (Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Day 12 (n=67, 65, 67, 73, 74, 73) | 54.95 percentage platelet reactive index (PRI) | Standard Deviation 18.86 |
| 75 mg Clopidogrel (Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline (n=68, 66, 67, 71, 72, 72) | 85.60 percentage platelet reactive index (PRI) | Standard Deviation 4.31 |
| 5 mg Prasugrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline (n=68, 66, 67, 71, 72, 72) | 86.10 percentage platelet reactive index (PRI) | Standard Deviation 5.31 |
| 5 mg Prasugrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Day 12 (n=67, 65, 67, 73, 74, 73) | 54.72 percentage platelet reactive index (PRI) | Standard Deviation 18.67 |
| 10 mg Prasugrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Day 12 (n=67, 65, 67, 73, 74, 73) | 27.74 percentage platelet reactive index (PRI) | Standard Deviation 15.84 |
| 10 mg Prasugrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline (n=68, 66, 67, 71, 72, 72) | 86.18 percentage platelet reactive index (PRI) | Standard Deviation 5.32 |
| 75 mg Clopidogrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Day 12 (n=67, 65, 67, 73, 74, 73) | 54.53 percentage platelet reactive index (PRI) | Standard Deviation 21.82 |
| 75 mg Clopidogrel (Non-Elderly) | Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy | Baseline (n=68, 66, 67, 71, 72, 72) | 86.18 percentage platelet reactive index (PRI) | Standard Deviation 5.32 |
Secondary
Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy
The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in P2Y12 reaction units (PRU). PRU report the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of the rate and extent of platelet aggregation in the presence of adenosine phosphate ADP. A lower PRU reflects stronger inhibition of P2Y12, whereas a higher PRU reflects weaker inhibition of P2Y12.
Time frame: Baseline, Day 12
Population: All randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable pharmacodynamic (PD) measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Prasugrel (Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline | 315.63 P2Y12 reaction units (PRU) | Standard Deviation 45.98 |
| 5 mg Prasugrel (Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Day 12 (n=71, 67, 69, 77, 79, 79) | 175.52 P2Y12 reaction units (PRU) | Standard Deviation 57.19 |
| 10 mg Prasugrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline | 314.11 P2Y12 reaction units (PRU) | Standard Deviation 45.74 |
| 10 mg Prasugrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Day 12 (n=71, 67, 69, 77, 79, 79) | 84.13 P2Y12 reaction units (PRU) | Standard Deviation 47.72 |
| 75 mg Clopidogrel (Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline | 314.14 P2Y12 reaction units (PRU) | Standard Deviation 44.54 |
| 75 mg Clopidogrel (Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Day 12 (n=71, 67, 69, 77, 79, 79) | 212.33 P2Y12 reaction units (PRU) | Standard Deviation 69.65 |
| 5 mg Prasugrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline | 291.81 P2Y12 reaction units (PRU) | Standard Deviation 45.16 |
| 5 mg Prasugrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Day 12 (n=71, 67, 69, 77, 79, 79) | 177.01 P2Y12 reaction units (PRU) | Standard Deviation 67.29 |
| 10 mg Prasugrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline | 291.62 P2Y12 reaction units (PRU) | Standard Deviation 44.9 |
| 10 mg Prasugrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Day 12 (n=71, 67, 69, 77, 79, 79) | 85.46 P2Y12 reaction units (PRU) | Standard Deviation 60.24 |
| 75 mg Clopidogrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Baseline | 291.62 P2Y12 reaction units (PRU) | Standard Deviation 44.9 |
| 75 mg Clopidogrel (Non-Elderly) | Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy | Day 12 (n=71, 67, 69, 77, 79, 79) | 181.22 P2Y12 reaction units (PRU) | Standard Deviation 71.8 |