Coronary Artery Disease
Conditions
Keywords
Platelet function
Brief summary
The 5-milligram (mg) dose of prasugrel in low body weight (LBW) patients with coronary artery disease produces a pharmacodynamic response within the same therapeutic range as 10-mg dose in higher body weight (HBW) 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
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Subjects 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 * 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 * 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 subjects 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 From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1) | Baseline, Day 12 | MPA to 20 micromolar (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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline, Day 12 | VASP phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition and were used to compare prasugrel versus clopidogrel, in low body weight (LBW) participants compared to higher body weight (HBW) participants. PRI was calculated by VASP. The PRI indicates the level of P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12 receptor thus stronger platelet inhibition, whereas a higher PRI reflects weaker inhibition of P2Y12 receptor and weaker platelet inhibition. |
| Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline, Day 12 | The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in PRU. PRU indicates the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of rate and extent of platelet aggregation in an adenosine phosphate (ADP)-containing channel of the device. A lower PRU reflects stronger inhibition of platelet aggregation, whereas a higher PRU reflects weaker inhibition of platelet aggregation. |
| Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | baseline (pre-dose) up to 4 hours post-dose | A pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing MPA (LTA) and AUC was conducted as originally intended, however the graphic output 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) at Day 12 of Therapy | Baseline , Day 12 | MPA to 20 micromolar (μM) adenosine diphosphate (ADP) was assessed by LTA, an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing 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 |
|---|---|
| Dose Sequence: Pras 5mg, Pras 10mg, Clop 75mg (LBW) Participants in the low body weight (LBW; \<60 kilograms \[kg\]) group received 5 milligrams (mg) of Prasugrel (Pras) during Study Period 1, followed by 10 mg Pras in Study Period 2, followed by 75 mg clopidogrel (Clop) in Study Period 3. | 17 |
| Dose Sequence: Pras 5mg, Clop 75 mg, Pras 10mg (LBW) Participants in the LBW group received 5 mg Pras during Study Period 1, followed by 75 mg Clop in Study Period 2, and 10 mg Pras in Study Period 3. | 17 |
| Dose Sequence: Pras 10mg, Pras 5mg, Clop 75 mg (HBW) Participants in the higher body weight (HBW; ≥60 kg) group received 10 mg Pras during Study Period 1, followed by 5 mg Pras in Study Period 2, followed by 75 mg Clop in Study Period 3. | 21 |
| Dose Sequence: Pras 10mg, Clop 75 mg, Pras 5mg (HBW) Participants in the HBW group received 10 mg Pras during Study Period 1, followed by 5 mg Pras in Study Period 2, followed by 75 mg Clop in Study Period 3. | 17 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1-Randomization up Through Day 12 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Dose Sequence: Pras 5mg, Pras 10mg, Clop 75mg (LBW) | Total | Dose Sequence: Pras 10mg, Clop 75 mg, Pras 5mg (HBW) | Dose Sequence: Pras 10mg, Pras 5mg, Clop 75 mg (HBW) | Dose Sequence: Pras 5mg, Clop 75 mg, Pras 10mg (LBW) |
|---|---|---|---|---|---|
| Age Continuous | 61.3 years STANDARD_DEVIATION 8.07 | 62.6 years STANDARD_DEVIATION 8.15 | 64.6 years STANDARD_DEVIATION 6.91 | 61.4 years STANDARD_DEVIATION 9.57 | 63.2 years STANDARD_DEVIATION 7.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 37 Participants | 8 Participants | 11 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 35 Participants | 9 Participants | 10 Participants | 9 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 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 17 Participants | 67 Participants | 14 Participants | 20 Participants | 16 Participants |
| Region of Enrollment Ireland | 2 participants | 18 participants | 6 participants | 8 participants | 2 participants |
| Region of Enrollment Netherlands | 9 participants | 27 participants | 5 participants | 5 participants | 8 participants |
| Region of Enrollment Sweden | 6 participants | 23 participants | 4 participants | 6 participants | 7 participants |
| Region of Enrollment United States | 0 participants | 4 participants | 2 participants | 2 participants | 0 participants |
| Sex: Female, Male Female | 15 Participants | 41 Participants | 5 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 31 Participants | 12 Participants | 14 Participants | 3 Participants |
| Tobacco Use Status Tobacco Use No | 10 participants | 48 participants | 13 participants | 16 participants | 9 participants |
| Tobacco Use Status Tobacco Use Yes | 7 participants | 24 participants | 4 participants | 5 participants | 8 participants |
| Weight | 56.06 kilograms (kg) STANDARD_DEVIATION 4.575 | 71.33 kilograms (kg) STANDARD_DEVIATION 17.98 | 85.96 kilograms (kg) STANDARD_DEVIATION 11.898 | 83.60 kilograms (kg) STANDARD_DEVIATION 17.146 | 56.78 kilograms (kg) STANDARD_DEVIATION 2.619 |
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 / 34 | 21 / 33 | 14 / 32 | 10 / 36 | 12 / 38 | 14 / 37 |
| serious Total, serious adverse events | 0 / 34 | 1 / 33 | 0 / 32 | 0 / 36 | 0 / 38 | 0 / 37 |
Outcome results
Primary
Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1)
MPA to 20 micromolar (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 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: Primary intent-to-treat (ITT) pharmacodynamic (PD) population: all randomized participants who continued in the study through Day 12, and had at least 1 evaluable PD assessment at Day 12. Participants were analyzed based on the treatment group they were randomized to irrespective to the treatment they received.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prasugrel 5 mg (LBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1) | Baseline | 75.00 percent aggregation |
| Prasugrel 5 mg (LBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1) | Day 12 (n=32, 37) | 47.00 percent aggregation |
| Prasugrel 10 mg (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1) | Day 12 (n=32, 37) | 47.00 percent aggregation |
| Prasugrel 10 mg (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1) | Baseline | 76.40 percent aggregation |
p-value: 0.52695% CI: [-23.4, 0.2]bootstrap (to determine 95% CI)
Secondary
Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy
MPA to 20 micromolar (μM) adenosine diphosphate (ADP) was assessed by LTA, an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing 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: As-treated pharmacodynamic (PD) population: all randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable 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 |
|---|---|---|---|---|
| Prasugrel 5 mg (LBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Day 12 ( n= 32,32,31,35,37,35) | 48.10 percent aggregation | Standard Deviation 13.89 |
| Prasugrel 5 mg (LBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Baseline | 76.27 percent aggregation | Standard Deviation 9.49 |
| Prasugrel 10 mg (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Day 12 ( n= 32,32,31,35,37,35) | 38.11 percent aggregation | Standard Deviation 14.17 |
| Prasugrel 10 mg (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Baseline | 76.20 percent aggregation | Standard Deviation 9.63 |
| 75 mg Clopidogrel (LBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Day 12 ( n= 32,32,31,35,37,35) | 51.41 percent aggregation | Standard Deviation 13.56 |
| 75 mg Clopidogrel (LBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Baseline | 76.20 percent aggregation | Standard Deviation 9.63 |
| 5 mg Prasugrel (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Baseline | 77.63 percent aggregation | Standard Deviation 12.29 |
| 5 mg Prasugrel (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Day 12 ( n= 32,32,31,35,37,35) | 61.90 percent aggregation | Standard Deviation 18.93 |
| 10 mg Prasugrel (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Day 12 ( n= 32,32,31,35,37,35) | 47.92 percent aggregation | Standard Deviation 15.18 |
| 10 mg Prasugrel (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Baseline | 77.93 percent aggregation | Standard Deviation 12.27 |
| 75 mg Clopidogrel (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Day 12 ( n= 32,32,31,35,37,35) | 65.28 percent aggregation | Standard Deviation 17.83 |
| 75 mg Clopidogrel (HBW) | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy | Baseline | 77.63 percent aggregation | Standard Deviation 12.29 |
Secondary
Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy
VASP phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition and were used to compare prasugrel versus clopidogrel, in low body weight (LBW) participants compared to higher body weight (HBW) participants. PRI was calculated by VASP. The PRI indicates the level of P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12 receptor thus stronger platelet inhibition, whereas a higher PRI reflects weaker inhibition of P2Y12 receptor and weaker platelet inhibition.
Time frame: Baseline, Day 12
Population: As-treated pharmacodynamic (PD) population: all randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable 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 |
|---|---|---|---|---|
| Prasugrel 5 mg (LBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline | 86.57 percentage PRI | Standard Deviation 4.44 |
| Prasugrel 5 mg (LBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Day 12 (n=32,31,30,32,36,34) | 33.54 percentage PRI | Standard Deviation 15.77 |
| Prasugrel 10 mg (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Day 12 (n=32,31,30,32,36,34) | 15.09 percentage PRI | Standard Deviation 11.71 |
| Prasugrel 10 mg (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline | 86.44 percentage PRI | Standard Deviation 4.45 |
| 75 mg Clopidogrel (LBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline | 86.44 percentage PRI | Standard Deviation 4.45 |
| 75 mg Clopidogrel (LBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Day 12 (n=32,31,30,32,36,34) | 39.01 percentage PRI | Standard Deviation 17.49 |
| 5 mg Prasugrel (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline | 86.77 percentage PRI | Standard Deviation 3.42 |
| 5 mg Prasugrel (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Day 12 (n=32,31,30,32,36,34) | 56.87 percentage PRI | Standard Deviation 15.47 |
| 10 mg Prasugrel (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Day 12 (n=32,31,30,32,36,34) | 27.79 percentage PRI | Standard Deviation 18.13 |
| 10 mg Prasugrel (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline | 86.76 percentage PRI | Standard Deviation 3.37 |
| 75 mg Clopidogrel (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Day 12 (n=32,31,30,32,36,34) | 56.35 percentage PRI | Standard Deviation 18.33 |
| 75 mg Clopidogrel (HBW) | Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy | Baseline | 86.77 percentage PRI | Standard Deviation 3.42 |
Secondary
Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy
The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in PRU. PRU indicates the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of rate and extent of platelet aggregation in an adenosine phosphate (ADP)-containing channel of the device. A lower PRU reflects stronger inhibition of platelet aggregation, whereas a higher PRU reflects weaker inhibition of platelet aggregation.
Time frame: Baseline, Day 12
Population: As-treated pharmacodynamic (PD) population: all randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable 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 |
|---|---|---|---|---|
| Prasugrel 5 mg (LBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline | 317.9 P2Y12 reaction units (PRU) | Standard Deviation 46.1 |
| Prasugrel 5 mg (LBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Day 12 (n=32,31,32,35,34,34) | 129.5 P2Y12 reaction units (PRU) | Standard Deviation 62.14 |
| Prasugrel 10 mg (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Day 12 (n=32,31,32,35,34,34) | 55.9 P2Y12 reaction units (PRU) | Standard Deviation 38.08 |
| Prasugrel 10 mg (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline | 315.3 P2Y12 reaction units (PRU) | Standard Deviation 44.26 |
| 75 mg Clopidogrel (LBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline | 315.3 P2Y12 reaction units (PRU) | Standard Deviation 44.26 |
| 75 mg Clopidogrel (LBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Day 12 (n=32,31,32,35,34,34) | 151.7 P2Y12 reaction units (PRU) | Standard Deviation 57.46 |
| 5 mg Prasugrel (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline | 312.8 P2Y12 reaction units (PRU) | Standard Deviation 43.01 |
| 5 mg Prasugrel (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Day 12 (n=32,31,32,35,34,34) | 193.9 P2Y12 reaction units (PRU) | Standard Deviation 74.09 |
| 10 mg Prasugrel (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline | 311.0 P2Y12 reaction units (PRU) | Standard Deviation 43.76 |
| 10 mg Prasugrel (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Day 12 (n=32,31,32,35,34,34) | 102.1 P2Y12 reaction units (PRU) | Standard Deviation 69.49 |
| 75 mg Clopidogrel (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Day 12 (n=32,31,32,35,34,34) | 207.0 P2Y12 reaction units (PRU) | Standard Deviation 67.62 |
| 75 mg Clopidogrel (HBW) | Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy | Baseline | 312.8 P2Y12 reaction units (PRU) | Standard Deviation 43.01 |
Secondary
Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC)
A pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing MPA (LTA) and AUC was conducted as originally intended, however the graphic output 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 (pre-dose) 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 |
|---|---|---|---|
| Prasugrel 5 mg (LBW) | Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | 28.9 nanogram•hour/milliliter (ng•hr/mL) | Geometric Coefficient of Variation 37 |
| Prasugrel 10 mg (HBW) | Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | 59.3 nanogram•hour/milliliter (ng•hr/mL) | Geometric Coefficient of Variation 40 |
| 75 mg Clopidogrel (LBW) | Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | 18.4 nanogram•hour/milliliter (ng•hr/mL) | Geometric Coefficient of Variation 38 |
| 5 mg Prasugrel (HBW) | Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | 19.4 nanogram•hour/milliliter (ng•hr/mL) | Geometric Coefficient of Variation 46 |
| 10 mg Prasugrel (HBW) | Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | 46.7 nanogram•hour/milliliter (ng•hr/mL) | Geometric Coefficient of Variation 44 |
| 75 mg Clopidogrel (HBW) | Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC) | 12.7 nanogram•hour/milliliter (ng•hr/mL) | Geometric Coefficient of Variation 60 |