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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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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)..
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prasugrel Maintenance Dose | Experimental | Prasugrel 10 mg QD MD |
|
| Ticagrelor Maintenance Dose | Active Comparator | Ticagrelor 90 mg twice-daily (BID) MD |
|
| Prasugrel Loading Dose | Experimental | Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prasugrel Loading Dose | Drug | 60mg given as six 10mg film coated tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 7 days after first randomized dose |
| Measure | Description | Time Frame |
|---|---|---|
| P2Y12 Reaction Units | P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay measured at 2, 4, 24, 48 hours after first randomized study treatment | 2, 4, 24, 48 hours after first randomized dose |
| Platelet Reactivity Index |
Not provided
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:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Univ. of Florida College Medicine | Jacksonville | Florida | 32209 | United States | ||
| Clinical Pharmacology Unit of Miami |
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
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
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| Prasugrel Maintenance Dose | Drug | 10mg maintenance dose, given as one 10mg film coated tablet |
|
|
| Ticagrelor Maintenance Dose | Drug | one 90mg film coated tablet |
|
|
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.
| 2, 4, 24, 48 hours, 7 days after first randomized dose |
| 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. | 2, 4, 24, 48 hours, 7 days after first randomized dose |
| 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. | 2, 4, 24, 48 hours, 7 days after first randomized dose |
| 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 | 2, 4, 24, 48 hours, 7 days after first randomized dose |
| Miami |
| Florida |
| 33014 |
| United States |
| Progressive Medical Research | Port Orange | Florida | 32127 | United States |
| Sinai Center for Thrombosis Research | Baltimore | Maryland | 21215 | United States |
| Medpace Clinical Pharmacology Unit | Cincinnati | Ohio | 45212 | United States |
| Black Hills Cardiovascular Research | Rapid City | South Dakota | 57701 | United States |
| West Houston Area Clinical Trial Consultants | Houston | Texas | 77094 | United States |
| Cardiology Center of Houston | Katy | Texas | 77450 | United States |
| University Hospital of Wales | Heathpark | Cardiff | CF14 4XW | United Kingdom |
| Bristol Heart Institute | Bristol | B52 8HW | United Kingdom |
| University Hospital Leicester | Leicester | LE3 9QP | United Kingdom |
| Southampton General Hospital | Southampton | SO16 6YD | United Kingdom |
| New Cross Hospital | Wolverhampton | WV10 0QP | United Kingdom |
| Prasugrel Maintenance Dose |
Prasugrel 10 mg QD MD Prasugrel Maintenance Dose : 10mg maintenance dose, given as one 10mg film coated tablet |
| FG002 | Ticagrelor Maintenance Dose | Ticagrelor 90 mg twice-daily (BID) MD Ticagrelor Maintenance Dose : one 90mg film coated tablet |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Prasugrel Maintenance Dose | Prasugrel 10 mg QD MD Prasugrel Maintenance Dose : 10mg maintenance dose, given as one 10mg film coated tablet |
| BG002 | Ticagrelor Maintenance Dose | Ticagrelor 90 mg twice-daily (BID) MD Ticagrelor Maintenance Dose : one 90mg film coated tablet |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| weight | Mean | Standard Deviation | kg |
| |||||||||||||||
| height | Mean | Standard Deviation | cm |
| |||||||||||||||
| body mass index | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| diabetes mellitus history | number of participants with diabetes mellitus sum of categories does not equal number of participants due to not all participants having this specific medical condition | Number | participants |
| |||||||||||||||
| hypertension history | number of participants with hypertension susum of categories does not equal number of participants due to not all participants having this specific medical condition | Number | participants |
| |||||||||||||||
| hyperlipidemia history | number of participants with hyperlipidemia sum of categories does not equal number of participants due to not all participants having this specific medical condition | Number | participants |
| |||||||||||||||
| peripheral artery disease history | number of participants with peripheral artery disease (PAD) sum of categories does not equal number of participants due to not all participants having this specific medical condition | Number | participants |
| |||||||||||||||
| body mass index category | body mass index <30 kg/m^2 or >= 30 kg/m^2 sum of categories does not equal number of participants due to missing data for 1 subject | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | Standard Error | PRU (P2Y12 Reaction Units) | 7 days after first randomized dose |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | Primary Population | Posted | Least Squares Mean | Standard Error | PRU | 2, 4, 24, 48 hours after first randomized dose |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | Primary Population | Posted | Least Squares Mean | Standard Error | percentage PRI | 2, 4, 24, 48 hours, 7 days after first randomized dose |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | Primary population | Posted | Least Squares Mean | Standard Error | percent inhibition | 2, 4, 24, 48 hours, 7 days after first randomized dose |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | Primary population | Posted | Least Squares Mean | Standard Error | Percent Inhibition | 2, 4, 24, 48 hours, 7 days after first randomized dose |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | Primary population | Posted | Number | percentage of subjects | 2, 4, 24, 48 hours, 7 days after first randomized dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 34 | 8 | 34 | ||
| EG001 | Prasugrel Maintenance Dose | Prasugrel 10 mg QD MD Prasugrel Maintenance Dose : 10mg maintenance dose, given as one 10mg film coated tablet | 0 | 41 | 10 | 41 | ||
| EG002 | Ticagrelor Maintenance Dose | Ticagrelor 90 mg twice-daily (BID) MD Ticagrelor Maintenance Dose : one 90mg film coated tablet | 1 | 35 | 12 | 35 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| congestive heart failure | Cardiac disorders |
| |||
| depression | Nervous system disorders |
| |||
| pneumonia | Respiratory, thoracic and mediastinal disorders |
| |||
| alcohol poisoning | Injury, poisoning and procedural complications |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| eccymosis | Skin and subcutaneous tissue disorders |
| |||
| headache | Nervous system disorders |
| |||
| upper respiratory tract infection | Infections and infestations |
| |||
| dyspnoea | Respiratory, thoracic and mediastinal disorders |
| |||
| diarrhoea | Gastrointestinal disorders |
| |||
| periodontal disease | Gastrointestinal disorders |
| |||
| arthralgia | Musculoskeletal and connective tissue disorders |
| |||
| costochondritis | Musculoskeletal and connective tissue disorders |
| |||
| pain in extremity | Musculoskeletal and connective tissue disorders |
| |||
| angina pectoris | Cardiac disorders |
| |||
| vision blurred | Eye disorders |
| |||
| allergic oedema | Immune system disorders |
| |||
| nasopharyngitis | Infections and infestations |
| |||
| alanine aminotransferase increased | Investigations |
| |||
| hypomagnesaemia | Metabolism and nutrition disorders |
| |||
| renal failure | Renal and urinary disorders |
| |||
| injection site haematoma | General disorders |
| |||
| laceration | Injury, poisoning and procedural complications |
| |||
| muscle strain | Injury, poisoning and procedural complications |
| |||
| epistaxis | Respiratory, thoracic and mediastinal disorders |
|
Consultants may not publish in any way without the prior written consent of Daiichi Sankyo Inc., which consent may be witheld by DSI in its sole discretion, any material or manuscript relating to Consultant's work hereunder and/or any information or materials that Consultant received in connection with or pursuant to this Agreement or Consultant's relationship established with DSI.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fred Lipkin | Daiichi Sankyo Medical Affairs | 973-944-2216 | flipkin@dsi.com |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068799 | Prasugrel Hydrochloride |
| D000077486 | Ticagrelor |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United Kingdom |
|
| >= 30 kg/m^2 |
|
| Unknown |
|
|
prasugrel 10 mg QD for 7 days
|
|
prasugrel 10 mg QD for 7 days
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
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| Units | Counts |
|---|---|
| Participants |
|
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