Coronary Artery Disease
Conditions
Keywords
CAD, prasugrel, ticagrelor, antiplatelet, thienopyridine, P2Y12 Inhibitors
Brief summary
This is a Phase 4, multicenter, open-label (blinded Pharmacodynamic PD results), randomized, 3-arm, parallel-design study of subjects with stable Coronary Artery Disease CAD. This study will compare the PD effect of prasugrel 10 mg QD (once-daily) maintenance dose with ticagrelor 90 mg BID (twice daily) maintenance dose in subjects with stable CAD who have previously received ticagrelor loading does (LD) and maintenance dose (MD)..
Interventions
DRUGPrasugrel Loading Dose
60mg given as six 10mg film coated tablets
DRUGPrasugrel Maintenance Dose
10mg maintenance dose, given as one 10mg film coated tablet
one 90mg film coated tablet
Sponsors
Eli Lilly and Company
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Male or female; age \>= 18 and \< 75 years * Weight \>= 60 kg * Receiving low dose ASA (75 mg to 150 mg daily) for at least 7 days at the time of Visit 1 and able to continue the same regimen throughout the study * Stable CAD. CAD is defined as any of the following: * History of a positive stress test * Previous coronary revascularization including percutaneous coronary intervention (PCI), stent, or coronary artery bypass graft (CABG) * Angiographic demonstration of CAD (at least 1 lesion \>= 50 percent) * Presence of at least moderate plaque by computed tomography (CT) angiography * Electron beam CT coronary artery calcification score \>= 100 Agatston units * If female, may be enrolled if One of the following 3 criteria are met: * Had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form (ICF) * Post-menopausal for at least 1 year * If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy * Able and willing to provide written informed consent before entering the study
Exclusion criteria
* Have a defined need for adenosine diphosphate (ADP)-receptor inhibitor therapy, such as any of the following (or any other condition that in the Investigator's judgment would require such therapy): * Within =\< 12 months of an acute coronary syndrome (ACS) event (unstable angina \[UA\], non-ST-elevation myocardial infarction \[NSTEMI\], or ST-elevation myocardial infarction \[STEMI\]) regardless of initial treatment (that is, invasive versus noninvasive) * Subjects who underwent angioplasty within 12 months including bare-metal stent and/or a drug-eluting stent * Had any stent placed in an unprotected left main coronary artery or in the last patent artery within the last 12 months * Received thienopyridine therapy within 30 days of study entry * Plan to undergo coronary revascularization at any time during the trial * Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry) * History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope) * History or evidence of congestive heart failure (New York Heart Association Class III or above =\< 6 months before screening * Severe hepatic impairment * History of uric acid nephropathy * Uncontrolled hypertension, or systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg at screening * Severely impaired renal function (glomerular filtration rate \< 30 mL/minute) or on dialysis * At risk for bleeding * Taking prohibited medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P2Y12 Reaction Units | 7 days after first randomized dose | P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. Platelet aggregation with this system is defined by PRU, with a higher PRU indicative of greater platelet aggregation, and a lower PRU indicative of inhibition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| P2Y12 Reaction Units | 2, 4, 24, 48 hours after first randomized dose | P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment |
| Platelet Reactivity Index | 2, 4, 24, 48 hours, 7 days after first randomized dose | Platelet Reactivity Index (PRI) by the Vasodilator-Stimulated Phosphoprotein(VASP) assay 2, 4, 24, 48 hours and 7 days after first randomized study treatment. The VASP assay is an indirect, but relatively specific measure of inhibition of P2Y12-induced platelet activation. The assay quantifies the level of phosphorylation of the intracellular protein VASP, which undergoes phosphorylation when platelet P2Y12 receptors are blocked. The level of VASP phosphorylation, expressed as the PRI, represents the percentage inhibition relative to an assay baseline/maximal P2Y12-independent platelet aggregation. |
| PRU Percent Inhibition (Device-reported) | 2, 4, 24, 48 hours, 7 days after first randomized dose | PRU VerifyNow P2Y12 assay device-reported percent inhibition 2, 4, 24, and 48 hours, and 7 days after first randomized study treatment VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. The percent inhibition reported by VerifyNow device represents the percentage inhibition relative to maximal P2Y12-independent platelet aggregation achieved with the same sample in the presence of the iso-thrombin receptor activating peptide. |
| PRU Percent Inhibition (Calculated) | 2, 4, 24, 48 hours, 7 days after first randomized dose | Analysis of Mean Calculated Percent Inhibition by time point Calculated percent inhibition at time point t is defined as: 100 × (baseline PRU - PRUt)/baseline PRU where baseline PRU is the VerifyNow PRU value at pre-run-in baseline and PRUt is the VerifyNow PRU value at time t. |
| Percentage of Subjects With High On-treatment Platelet Reactivity | 2, 4, 24, 48 hours, 7 days after first randomized dose | Percentage of subjects with High on-treatment Platelet Reactivity (HPR) defined as a) \>= 208 PRU and b) \>= 230 PRU by the VerifyNow P2Y12 assay and c) \>50% PRI by the VASP assay, 2, 4, 24, and 48 hours and 7 days after first randomized study treatment. A poor response of the platelets to drug, called High Residual Platelet Reactivity (HRPR), has been incriminated to account for a recurrence of ischemic events |
Countries
United Kingdom, United States
Participant flow
Recruitment details
All subjects must have been taking low dose aspirin (ASA) (75 mg to 150 mg once daily-QD) for at least 7 days prior to Screening (Visit 1), and must have continued the same regimen throughout the study.
Pre-assignment details
The study consisted of a 3 to 5 day ticagrelor run-in phase followed by randomized treatment on 1 of 2 prasugrel regimens or continued ticagrelor
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Loading Dose Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)
Prasugrel Maintenance Dose : 10mg maintenance dose, given as one 10mg film coated tablet
Prasugrel Loading Dose : 60mg given as six 10mg film coated tablets | 34 |
| Prasugrel Maintenance Dose Prasugrel 10 mg QD MD
Prasugrel Maintenance Dose : 10mg maintenance dose, given as one 10mg film coated tablet | 41 |
| Ticagrelor Maintenance Dose Ticagrelor 90 mg twice-daily (BID) MD
Ticagrelor Maintenance Dose : one 90mg film coated tablet | 35 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Prasugrel Loading Dose | Prasugrel Maintenance Dose | Ticagrelor Maintenance Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 13 Participants | 13 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 28 Participants | 22 Participants | 74 Participants |
| Age, Continuous | 57.8 years STANDARD_DEVIATION 9.69 | 58.5 years STANDARD_DEVIATION 8.84 | 61.5 years STANDARD_DEVIATION 6.87 | 59.2 years STANDARD_DEVIATION 8.62 |
| body mass index | 33.2 kg/m^2 STANDARD_DEVIATION 5.88 | 32.3 kg/m^2 STANDARD_DEVIATION 5.92 | 29.2 kg/m^2 STANDARD_DEVIATION 4.82 | 31.6 kg/m^2 STANDARD_DEVIATION 5.77 |
| body mass index category < 30 kg/m^2 | 13 participants | 16 participants | 24 participants | 53 participants |
| body mass index category >= 30 kg/m^2 | 21 participants | 24 participants | 11 participants | 56 participants |
| body mass index category Unknown | 0 participants | 1 participants | 0 participants | 1 participants |
| diabetes mellitus history | 14 participants | 12 participants | 5 participants | 31 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 36 Participants | 30 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| height | 171.2 cm STANDARD_DEVIATION 8.74 | 171.9 cm STANDARD_DEVIATION 10.15 | 174.3 cm STANDARD_DEVIATION 9.14 | 172.4 cm STANDARD_DEVIATION 9.41 |
| hyperlipidemia history | 32 participants | 35 participants | 31 participants | 98 participants |
| hypertension history | 26 participants | 29 participants | 24 participants | 79 participants |
| peripheral artery disease history | 2 participants | 1 participants | 2 participants | 5 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 7 Participants | 4 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 33 Participants | 30 Participants | 89 Participants |
| Region of Enrollment United Kingdom | 4 participants | 5 participants | 3 participants | 12 participants |
| Region of Enrollment United States | 30 participants | 36 participants | 32 participants | 98 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 8 Participants | 29 Participants |
| Sex: Female, Male Male | 24 Participants | 30 Participants | 27 Participants | 81 Participants |
| weight | 97.0 kg STANDARD_DEVIATION 17.7 | 95.4 kg STANDARD_DEVIATION 18.85 | 89.4 kg STANDARD_DEVIATION 19.35 | 94.0 kg STANDARD_DEVIATION 18.77 |
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 | 8 / 34 | 10 / 41 | 12 / 35 |
| serious Total, serious adverse events | 0 / 34 | 0 / 41 | 1 / 35 |
Outcome results
Primary
P2Y12 Reaction Units
P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. Platelet aggregation with this system is defined by PRU, with a higher PRU indicative of greater platelet aggregation, and a lower PRU indicative of inhibition.
Time frame: 7 days after first randomized dose
Population: Primary Population includes all subjects who received at least 1 dose of randomized study drug and have valid PRU data at both randomization visit pre-dosing and end-of-treatment visit. A subject is considered to have valid PRU data for primary PD analyses if he/she does not have certain protocol deviations listed in Statistical Analysis Plan.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel Combined Groups | P2Y12 Reaction Units | 95.0 PRU (P2Y12 Reaction Units) | Standard Error 6.18 |
| Ticagrelor | P2Y12 Reaction Units | 49.0 PRU (P2Y12 Reaction Units) | Standard Error 8.68 |
Comparison: ANCOVA model included treatment as a main effect and pre-randomization baseline PRU as a covariate. The combined prasugrel groups were modeled as a single treatment. If the upper limit of the CI for the mean difference was not greater than 45 PRU, then the PD response to prasugrel 10 mg QD MD was deemed noninferior to that achieved by ticagrelor 90 mg BID MD.95% CI: [24.9, 67.2]
Secondary
P2Y12 Reaction Units
P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment
Time frame: 2, 4, 24, 48 hours after first randomized dose
Population: Primary Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel Combined Groups | P2Y12 Reaction Units | 48 hours | 159.3 PRU | Standard Error 7.68 |
| Prasugrel Combined Groups | P2Y12 Reaction Units | 2 hours | 33.7 PRU | Standard Error 3.18 |
| Prasugrel Combined Groups | P2Y12 Reaction Units | 24 hours | 126.8 PRU | Standard Error 7.57 |
| Prasugrel Combined Groups | P2Y12 Reaction Units | 4 hours | 41.1 PRU | Standard Error 3.67 |
| Ticagrelor | P2Y12 Reaction Units | 48 hours | 38.6 PRU | Standard Error 9.07 |
| Ticagrelor | P2Y12 Reaction Units | 24 hours | 47.6 PRU | Standard Error 8.71 |
| Ticagrelor | P2Y12 Reaction Units | 2 hours | 28.9 PRU | Standard Error 4.24 |
| Ticagrelor | P2Y12 Reaction Units | 4 hours | 29.3 PRU | Standard Error 4.54 |
| Prasugrel Loading Dose | P2Y12 Reaction Units | 48 hours | 118.3 PRU | Standard Error 9.22 |
| Prasugrel Loading Dose | P2Y12 Reaction Units | 24 hours | 81.6 PRU | Standard Error 8.86 |
| Prasugrel Loading Dose | P2Y12 Reaction Units | 4 hours | 24.1 PRU | Standard Error 4.69 |
| Prasugrel Loading Dose | P2Y12 Reaction Units | 2 hours | 22.1 PRU | Standard Error 4.22 |
| Prasugrel Maintenance Dose | P2Y12 Reaction Units | 2 hours | 44.8 PRU | Standard Error 4.15 |
| Prasugrel Maintenance Dose | P2Y12 Reaction Units | 48 hours | 199.0 PRU | Standard Error 9.07 |
| Prasugrel Maintenance Dose | P2Y12 Reaction Units | 24 hours | 167.8 PRU | Standard Error 8.44 |
| Prasugrel Maintenance Dose | P2Y12 Reaction Units | 4 hours | 57.0 PRU | Standard Error 4.53 |
Secondary
Percentage of Subjects With High On-treatment Platelet Reactivity
Percentage of subjects with High on-treatment Platelet Reactivity (HPR) defined as a) \>= 208 PRU and b) \>= 230 PRU by the VerifyNow P2Y12 assay and c) \>50% PRI by the VASP assay, 2, 4, 24, and 48 hours and 7 days after first randomized study treatment. A poor response of the platelets to drug, called High Residual Platelet Reactivity (HRPR), has been incriminated to account for a recurrence of ischemic events
Time frame: 2, 4, 24, 48 hours, 7 days after first randomized dose
Population: Primary population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 2 hours post dose | 0 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 4 hours post dose | 1.8 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 48 hours post dose | 22.2 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 24 hours post dose | 17.5 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 7 days post dose | 1.5 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 2 hours post dose | 3.5 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 48 hours post dose | 30.2 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 4 hours post dose | 0 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 48 hours post dose | 45 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 7 days post dose | 1.5 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 2 hours post dose | 0 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 24 hours post dose | 21.3 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 4 hours post dose | 0 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 7 days post dose | 15.5 percentage of subjects |
| Prasugrel Combined Groups | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 24 hours post dose | 14.3 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 24 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 4 hours post dose | 3.3 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 7 days post dose | 3 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 48 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 4 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 2 hours post dose | 3.3 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 24 hours post dose | 12.9 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 7 days post dose | 3 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 24 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 4 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 7 days post dose | 3.4 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 48 hours post dose | 6.3 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 2 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 48 hours post dose | 0 percentage of subjects |
| Ticagrelor | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 2 hours post dose | 0 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 24 hours post dose | 3.3 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 2 hours post dose | 0 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 4 hours post dose | 0 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 24 hours post dose | 3.3 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 48 hours post dose | 16.1 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 7 days post dose | 3.2 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 2 hours post dose | 0 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 4 hours post dose | 0 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 48 hours post dose | 6.5 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 7 days post dose | 3.2 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 2 hours post dose | 3.6 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 4 hours post dose | 0 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 24 hours post dose | 3.4 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 48 hours post dose | 13.8 percentage of subjects |
| Prasugrel Loading Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 7 days post dose | 23.1 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 4 hours post dose | 0 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 4 hours post dose | 0 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 4 hours post dose | 3.4 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 2 hours post dose | 0 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 7 days post dose | 0 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 2 hours post dose | 0 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 24 hours post dose | 37.5 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 48 hours post dose | 43.8 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 208 PRU 24 hours post dose | 37.5 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 7 days post dose | 9.4 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 7 days post dose | 0 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 48 hours post dose | 37.5 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 48 hours post dose | 74.2 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >50% PRI by VASP assay 2 hours post dose | 3.4 percentage of subjects |
| Prasugrel Maintenance Dose | Percentage of Subjects With High On-treatment Platelet Reactivity | >= 230 PRU by VerifyNow P2Y12 24 hours post dose | 24.2 percentage of subjects |
Secondary
Platelet Reactivity Index
Platelet Reactivity Index (PRI) by the Vasodilator-Stimulated Phosphoprotein(VASP) assay 2, 4, 24, 48 hours and 7 days after first randomized study treatment. The VASP assay is an indirect, but relatively specific measure of inhibition of P2Y12-induced platelet activation. The assay quantifies the level of phosphorylation of the intracellular protein VASP, which undergoes phosphorylation when platelet P2Y12 receptors are blocked. The level of VASP phosphorylation, expressed as the PRI, represents the percentage inhibition relative to an assay baseline/maximal P2Y12-independent platelet aggregation.
Time frame: 2, 4, 24, 48 hours, 7 days after first randomized dose
Population: Primary Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel Combined Groups | Platelet Reactivity Index | 48 hours post-dose | 48.1 percentage PRI | Standard Error 2.58 |
| Prasugrel Combined Groups | Platelet Reactivity Index | 4 hours post-dose | 16.3 percentage PRI | Standard Error 1.58 |
| Prasugrel Combined Groups | Platelet Reactivity Index | 7 days post-dose | 33.5 percentage PRI | Standard Error 2.64 |
| Prasugrel Combined Groups | Platelet Reactivity Index | 24 hours post-dose | 34.3 percentage PRI | Standard Error 2.24 |
| Prasugrel Combined Groups | Platelet Reactivity Index | 2 hours post-dose | 18.2 percentage PRI | Standard Error 1.37 |
| Ticagrelor | Platelet Reactivity Index | 24 hours post-dose | 19.1 percentage PRI | Standard Error 2.71 |
| Ticagrelor | Platelet Reactivity Index | 48 hours post-dose | 18.7 percentage PRI | Standard Error 3.2 |
| Ticagrelor | Platelet Reactivity Index | 7 days post-dose | 19.8 percentage PRI | Standard Error 3.58 |
| Ticagrelor | Platelet Reactivity Index | 4 hours post-dose | 14.3 percentage PRI | Standard Error 2.06 |
| Ticagrelor | Platelet Reactivity Index | 2 hours post-dose | 13.2 percentage PRI | Standard Error 1.85 |
| Prasugrel Loading Dose | Platelet Reactivity Index | 24 hours post-dose | 24.2 percentage PRI | Standard Error 2.85 |
| Prasugrel Loading Dose | Platelet Reactivity Index | 2 hours post-dose | 15.8 percentage PRI | Standard Error 1.94 |
| Prasugrel Loading Dose | Platelet Reactivity Index | 4 hours post-dose | 11.4 percentage PRI | Standard Error 2.16 |
| Prasugrel Loading Dose | Platelet Reactivity Index | 48 hours post-dose | 38.0 percentage PRI | Standard Error 3.37 |
| Prasugrel Loading Dose | Platelet Reactivity Index | 7 days post-dose | 38.8 percentage PRI | Standard Error 3.87 |
| Prasugrel Maintenance Dose | Platelet Reactivity Index | 48 hours post-dose | 57.7 percentage PRI | Standard Error 3.3 |
| Prasugrel Maintenance Dose | Platelet Reactivity Index | 4 hours post-dose | 20.9 percentage PRI | Standard Error 2.08 |
| Prasugrel Maintenance Dose | Platelet Reactivity Index | 2 hours post-dose | 20.4 percentage PRI | Standard Error 1.87 |
| Prasugrel Maintenance Dose | Platelet Reactivity Index | 24 hours post-dose | 43.7 percentage PRI | Standard Error 2.74 |
| Prasugrel Maintenance Dose | Platelet Reactivity Index | 7 days post-dose | 29.1 percentage PRI | Standard Error 3.5 |
Secondary
PRU Percent Inhibition (Calculated)
Analysis of Mean Calculated Percent Inhibition by time point Calculated percent inhibition at time point t is defined as: 100 × (baseline PRU - PRUt)/baseline PRU where baseline PRU is the VerifyNow PRU value at pre-run-in baseline and PRUt is the VerifyNow PRU value at time t.
Time frame: 2, 4, 24, 48 hours, 7 days after first randomized dose
Population: Primary population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel Combined Groups | PRU Percent Inhibition (Calculated) | 48 hours post dose | 41.59 Percent Inhibition | Standard Error 2.911 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Calculated) | 4 hours post dose | 85.06 Percent Inhibition | Standard Error 1.319 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Calculated) | 7 days psot dose | 64.97 Percent Inhibition | Standard Error 2.336 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Calculated) | 24 hours post dose | 53.63 Percent Inhibition | Standard Error 2.851 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Calculated) | 2 hours post-dose | 88.22 Percent Inhibition | Standard Error 1.113 |
| Ticagrelor | PRU Percent Inhibition (Calculated) | 24 hours post dose | 81.86 Percent Inhibition | Standard Error 3.237 |
| Ticagrelor | PRU Percent Inhibition (Calculated) | 48 hours post dose | 85.06 Percent Inhibition | Standard Error 3.388 |
| Ticagrelor | PRU Percent Inhibition (Calculated) | 7 days psot dose | 80.69 Percent Inhibition | Standard Error 3.322 |
| Ticagrelor | PRU Percent Inhibition (Calculated) | 4 hours post dose | 89.26 Percent Inhibition | Standard Error 1.632 |
| Ticagrelor | PRU Percent Inhibition (Calculated) | 2 hours post-dose | 89.73 Percent Inhibition | Standard Error 1.476 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Calculated) | 24 hours post dose | 71.40 Percent Inhibition | Standard Error 3.291 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Calculated) | 2 hours post-dose | 92.55 Percent Inhibition | Standard Error 1.475 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Calculated) | 4 hours post dose | 91.36 Percent Inhibition | Standard Error 1.686 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Calculated) | 48 hours post dose | 57.98 Percent Inhibition | Standard Error 3.438 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Calculated) | 7 days psot dose | 64.97 Percent Inhibition | Standard Error 3.429 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Calculated) | 48 hours post dose | 26.20 Percent Inhibition | Standard Error 3.332 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Calculated) | 4 hours post dose | 79.35 Percent Inhibition | Standard Error 1.605 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Calculated) | 2 hours post-dose | 84.15 Percent Inhibition | Standard Error 1.429 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Calculated) | 24 hours post dose | 38.01 Percent Inhibition | Standard Error 3.085 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Calculated) | 7 days psot dose | 64.97 Percent Inhibition | Standard Error 3.221 |
Secondary
PRU Percent Inhibition (Device-reported)
PRU VerifyNow P2Y12 assay device-reported percent inhibition 2, 4, 24, and 48 hours, and 7 days after first randomized study treatment VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. The percent inhibition reported by VerifyNow device represents the percentage inhibition relative to maximal P2Y12-independent platelet aggregation achieved with the same sample in the presence of the iso-thrombin receptor activating peptide.
Time frame: 2, 4, 24, 48 hours, 7 days after first randomized dose
Population: Primary population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel Combined Groups | PRU Percent Inhibition (Device-reported) | 48 hours post-dose | 42.3 percent inhibition | Standard Error 2.79 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Device-reported) | 4 hours post-dose | 84.9 percent inhibition | Standard Error 1.25 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Device-reported) | 7 days post-dose | 65.5 percent inhibition | Standard Error 2.17 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Device-reported) | 24 hours post-dose | 54.1 percent inhibition | Standard Error 2.68 |
| Prasugrel Combined Groups | PRU Percent Inhibition (Device-reported) | 2 hours post-dose | 87.8 percent inhibition | Standard Error 1.13 |
| Ticagrelor | PRU Percent Inhibition (Device-reported) | 24 hours post-dose | 81.9 percent inhibition | Standard Error 3.13 |
| Ticagrelor | PRU Percent Inhibition (Device-reported) | 48 hours post-dose | 85.8 percent inhibition | Standard Error 3.19 |
| Ticagrelor | PRU Percent Inhibition (Device-reported) | 7 days post-dose | 81.0 percent inhibition | Standard Error 3.07 |
| Ticagrelor | PRU Percent Inhibition (Device-reported) | 4 hours post-dose | 89.6 percent inhibition | Standard Error 1.58 |
| Ticagrelor | PRU Percent Inhibition (Device-reported) | 2 hours post-dose | 89.2 percent inhibition | Standard Error 1.53 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Device-reported) | 24 hours post-dose | 69.6 percent inhibition | Standard Error 3.18 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Device-reported) | 2 hours post-dose | 91.4 percent inhibition | Standard Error 1.53 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Device-reported) | 4 hours post-dose | 90.2 percent inhibition | Standard Error 1.63 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Device-reported) | 48 hours post-dose | 58.3 percent inhibition | Standard Error 3.24 |
| Prasugrel Loading Dose | PRU Percent Inhibition (Device-reported) | 7 days post-dose | 65.6 percent inhibition | Standard Error 3.16 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Device-reported) | 48 hours post-dose | 26.8 percent inhibition | Standard Error 3.19 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Device-reported) | 4 hours post-dose | 79.8 percent inhibition | Standard Error 1.58 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Device-reported) | 2 hours post-dose | 84.3 percent inhibition | Standard Error 1.51 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Device-reported) | 24 hours post-dose | 40.0 percent inhibition | Standard Error 3.03 |
| Prasugrel Maintenance Dose | PRU Percent Inhibition (Device-reported) | 7 days post-dose | 65.4 percent inhibition | Standard Error 3.02 |