Coronary Artery Disease
Conditions
Keywords
thienopyridine, pharmacologic action, prasugrel, clopidogrel
Brief summary
The primary objective of the study is to describe the cumulative proportion of participants who return to baseline platelet P2Y12 receptor function over time (up to 12 days post last maintenance dose) following discontinuation of prasugrel 10 mg daily x 7 days assessed by Accumetrics VerifyNow P2Y12 reaction units (PRU) and described by Kaplan Meier curves. The primary analysis is descriptive and is intended to provide information relating to the return of baseline platelet function following discontinuation of maintenance therapy with either prasugrel or clopidogrel.
Interventions
DRUGPrasugrel
Prasugrel 10mg tablet administered once daily for 7 days. After a 1-day to 14-day screening period, participants will receive active treatment with either prasugrel or clopidogrel for 7 days. If a participant has not missed more than 1 dose of study medication and is unable to attend Visit 3 (Washout Day 1) the day after the 7th day of study medication, the participant may take up to an additional 3 days of study medication and proceed to Visit 3 the day after the last dose. Active treatment will be followed by a 1-day to 12-day Washout Period depending on the time to reach both of the exit criteria.
DRUGClopidogrel
Clopidogrel 75 mg tablet administered once daily for 7 days. After a 1-day to 14-day screening period, participants will receive active treatment with either prasugrel or clopidogrel for 7 days. If a participant has not missed more than 1 dose of study medication and is unable to attend Visit 3 (Washout Day 1) the day after the 7th day of study medication, the participant may take up to an additional 3 days of study medication and proceed to Visit 3 the day after the last dose. Active treatment will be followed by a 1-day to 12-day Washout Period depending on the time to reach both of the exit criteria.
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects \>/= 18 years and \<75 years of age * Weight \>/= 60 kg * On aspirin therapy (81 mg to 325 mg daily) at the time of screening and able to maintain a consistent aspirin dosing regimen from the baseline visit through the final study visit * Subjects who do not have contraindications for a thienopyridine (ie, prasugrel, clopidogrel or ticlopidine), and have a history of stable atherosclerosis represented by Coronary Artery disease, defined as any of the following: * chronic stable angina * Prior history of acute coronary syndrome (\>/= 30 days before screening) including unstable angina or acute myocardial infarction (ST elevation Myocardial Infarction \[STEMI\] or non-ST elevation Myocardial Infarction \[NSTEMI\]), not currently prescribed or currently on thienopyridine therapy; * Previous coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA), stent, or coronary artery bypass grafting (CABG) coronary artery disease (\>/= 50% obstruction) in at least one coronary vessel after angiography * Female subjects who meet one of the following: * Women of childbearing potential with a negative serum pregnancy test at screening who are not breast feeding, do not plan to become pregnant during the study, and agree to use an approved method of birth control during the study. Approved methods of birth control are oral, path, injectable or implantable hormonal contraception, intrauterine device, diaphragm plus spermicide, or female condom plus spermicide. Abstinence, partner's use of condoms, and partner's vasectomy are NOT acceptable methods of contraception. * Women who have been postmenopausal for at least 1 year or have had a hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation at least 6 months prior to signing the informed consent form. * Subjects with a competent mental condition to provide written informed consent before entering the study.
Exclusion criteria
* Any other formal indication for the use of a thienopyridine. * Subjects with a history of refractory ventricular arrhythmias. * Subjects with a history of an implantable defibrillator device. * Subjects with a history or evidence of congestive heart failure (New York Heart Association \[NYHA\] Class III or above) within 6 months prior to screening. * Subjects with significant hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) at either the time of screening or baseline assessment. * Bleeding Risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | up to 12 days after last dose | On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%. The results are expressed as cumulative percentage of participants. |
| The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | up to 12 days after last dose | On the first day of the Washout Period (visit 3), the blood draw for platelet function testing was obtained 24 hours (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | up to 12 days after last dose | On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/-6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%. |
| Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | up to 12 days after the last dose | On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hour (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to (\<=) 20%. |
| Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | up to 12 days after last dose | On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/-6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participants met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%. |
| Time to Return to Baseline PRU for the Primary Population Using the Primary Definition of Return to Baseline in Relation to the Inhibition of Platelet Aggregation 24 Hours Following the Last Maintenance Dose | up to 12 days after the last dose | Time to return to baseline PRU (\<= 60 units of baseline) dependent upon baseline PRU and platelet % inhibition on Washout Period Day 1 but independent of treatment. The following regression model was derived for predicting number of days to return to baseline PRU where PI(1) represents platelet percentage inhibition on Washout Day 1. Number days to return to baseline PRU derived from: Number days to return to baseline PRU=-3.350+0.079\*PI(1)+0.014\*baseline PRU. The predicted number of days to return to baseline based on device-derived platelet percentage inhibition is reported for each treatment group. |
| Percentage of Inhibition of Platelet Aggregation on Washout Day 1 | Washout Day 1 | Inhibition of platelet aggregation was assessed by Accumetrics VerifyNow® P2Y12 reaction units (PRU). On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hour (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%. |
| Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | up to 12 days after last dose | On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/-6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 4 sites in the US from 23 February 2010 to 24 May 2010 and 56 participants were randomized into the study. The study population consisted of male and female aspirin-treated participants with stable coronary artery disease, 18 to 75 years of age.
Pre-assignment details
The Overall Study Period included a 1-day to 14-day Screening Period, a 7-day Active Treatment Period, and a Washout Period of up to 12 days. Following the 1-day to 14-day Screening Period, eligible participants were randomized in a 1:1 ratio to either prasugrel or clopidogrel at Visit 2 (the first day of the Active Treatment Period).
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days. | 29 |
| Clopidogrel Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days. | 27 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Prasugrel | Total | Clopidogrel |
|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 8.45 | 59.80 Years STANDARD_DEVIATION 8.56 | 62.3 Years STANDARD_DEVIATION 8.1 |
| Alcohol Use Currently use alcohol | 19 participants 0 | 37 participants 0 | 18 participants 0 |
| Alcohol Use Formerly used alcohol | 7 participants 0 | 11 participants 0 | 4 participants 0 |
| Alcohol Use Never used alcohol | 3 participants 0 | 8 participants 0 | 5 participants 0 |
| Body Mass Index | 32.0 kg/m^2 STANDARD_DEVIATION 4.07 | 31.2 kg/m^2 STANDARD_DEVIATION 4.76 | 30.3 kg/m^2 STANDARD_DEVIATION 5.34 |
| Diabetes status Does not have diabetes | 18 participants 0 | 34 participants 0 | 16 participants 0 |
| Diabetes status Has diabetes | 11 participants 0 | 22 participants 0 | 11 participants 0 |
| Ethnicity Hispanic or Latino | 1 participants 0 | 1 participants 0 | 0 participants 0 |
| Ethnicity Non Hispanic or Latino | 28 participants 0 | 55 participants 0 | 27 participants 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 55 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 174.1 cm STANDARD_DEVIATION 8.2 | 173.8 cm STANDARD_DEVIATION 8.52 | 173.5 cm STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 44 Participants | 22 Participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 7 Participants |
| Sex: Female, Male Male | 25 Participants | 45 Participants | 20 Participants |
| Smoking Status Currently Smoke | 10 participants 0 | 16 participants 0 | 6 participants 0 |
| Smoking Status Formerly Smoked | 12 participants 0 | 23 participants 0 | 11 participants 0 |
| Smoking Status Never smoked | 7 participants 0 | 17 participants 0 | 10 participants 0 |
| weight | 97.3 kg STANDARD_DEVIATION 15.13 | 94.1 kg STANDARD_DEVIATION 15.02 | 90.8 kg STANDARD_DEVIATION 14.41 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 29 | 9 / 27 |
| serious Total, serious adverse events | 0 / 29 | 0 / 27 |
Outcome results
Primary
The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline
On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%. The results are expressed as cumulative percentage of participants.
Time frame: up to 12 days after last dose
Population: Participants in Primary Population defined as Baseline PRU-PRU less than or equal to 60 units (R-to-B). Primary Population included participants who entered Washout Period and had platelet function data at both baseline and Washout Period Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 1 | 0 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 3 | 3.6 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 5 | 37.0 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 6 | 62.9 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 7 | 77.8 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 9 | 100.0 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 7 | 96.2 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 1 | 30.8 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 6 | 96.2 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 3 | 53.9 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 9 | 100.0 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline | return to baseline PRU by washout day 5 | 84.6 cumulative percentage of participants |
Primary
The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline
On the first day of the Washout Period (visit 3), the blood draw for platelet function testing was obtained 24 hours (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%.
Time frame: up to 12 days after last dose
Population: Participants in Primary Population using secondary definition of return to baseline. Primary Population included participants who entered the Washout Period and had platelet function data at both baseline and Washout Period Day 1. Secondary definition of return to baseline was (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 1 | 0.0 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 3 | 0.0 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 5 | 37.0 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 6 | 55.6 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 7 | 77.8 cumulative percentage of participants |
| Prasugrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 9 | 100.0 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 7 | 96.2 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 1 | 30.8 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 6 | 88.5 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 3 | 53.9 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 9 | 100.0 cumulative percentage of participants |
| Clopidogrel | The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline | returned to baseline PRU by washout day 5 | 80.8 cumulative percentage of participants |
Secondary
Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population
On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/-6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participants met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%.
Time frame: up to 12 days after last dose
Population: Participants in Primary Population using primary definition of return to baseline. Primary population included participants who entered the Washout Period and had platelet function data at both baseline and Washout Period Day 1. Primary definition of return to baseline was (Baseline PRU-PRU) less than or equal to 60 units.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | Washout day 50% returned to baseline PRU | 6 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | Washout day 75% returned to baseline PRU | 7 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | Washout day 90% returned to baseline PRU | 9 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | Washout day 50% returned to baseline PRU | 3 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | Washout day 75% returned to baseline PRU | 5 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population | Washout day 90% returned to baseline PRU | 6 days |
Secondary
Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population
On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/-6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%.
Time frame: up to 12 days after last dose
Population: Participants in Primary Population using secondary definition of return to baseline. Primary Population included participants who entered Washout Period and had platelet function data at both baseline and Washout Period Day 1. Secondary definition of return to baseline was (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | Washout day 50% returned to baseline PRU | 6 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | Washout day 75% returned to baseline PRU | 7 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | Washout day 90% returned to baseline PRU | 9 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | Washout day 50% returned to baseline PRU | 3 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | Washout day 75% returned to baseline PRU | 5 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population | Washout day 90% returned to baseline PRU | 7 days |
Secondary
Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population
On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/-6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/Baseline PRU less than or equal to 20%.
Time frame: up to 12 days after last dose
Population: Participants in Responder Population using primary definition of R-to-B. Primary Population included participants who entered Washout Period and had platelet function data at baseline and Washout Day 1. Responder Population was Primary Population excluding poor pharmacodynamic responders. Primary definition of R-to-B was (Baseline PRU-PRU) less than or equal to 60 units.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | Washout day 50% returned to baseline PRU | 6 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | Washout day 75% returned to baseline PRU | 7 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | Washout day 90% returned to baseline PRU | 9 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | Washout day 50% returned to baseline PRU | 5 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | Washout day 75% returned to baseline PRU | 5 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population | Washout day 90% returned to baseline PRU | 6 days |
Secondary
Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population
On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hour (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to (\<=) 20%.
Time frame: up to 12 days after the last dose
Population: Participants in Responder Population using secondary definition of R-to-B. Primary Population included participants who entered Washout Period and had platelet function data at both baseline and Washout Period Day 1. Responder Population was Primary Population excluding poor pharmacodynamic responders. Secondary definition of R-to-B was (Baseline PRU-PRU)/ (Baseline PRU) \<= 20%.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | Washout day 50% returned to baseline PRU | 6 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | Washout day 75% returned to baseline PRU | 7 days |
| Prasugrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | Washout day 90% returned to baseline PRU | 9 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | Washout day 50% returned to baseline PRU | 5 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | Washout day 75% returned to baseline PRU | 6 days |
| Clopidogrel | Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population | Washout day 90% returned to baseline PRU | 7 days |
Secondary
Percentage of Inhibition of Platelet Aggregation on Washout Day 1
Inhibition of platelet aggregation was assessed by Accumetrics VerifyNow® P2Y12 reaction units (PRU). On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hour (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%.
Time frame: Washout Day 1
Population: Participants in the Primary Population. The Primary Population included participants who entered the Washout Period and had platelet function testing data at both baseline (Visit 2) and Washout Period Day 1 (Visit 3).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Percentage of Inhibition of Platelet Aggregation on Washout Day 1 | 72.3 percentage | Standard Deviation 11.78 |
| Clopidogrel | Percentage of Inhibition of Platelet Aggregation on Washout Day 1 | 35.4 percentage | Standard Deviation 23.35 |
Secondary
Time to Return to Baseline PRU for the Primary Population Using the Primary Definition of Return to Baseline in Relation to the Inhibition of Platelet Aggregation 24 Hours Following the Last Maintenance Dose
Time to return to baseline PRU (\<= 60 units of baseline) dependent upon baseline PRU and platelet % inhibition on Washout Period Day 1 but independent of treatment. The following regression model was derived for predicting number of days to return to baseline PRU where PI(1) represents platelet percentage inhibition on Washout Day 1. Number days to return to baseline PRU derived from: Number days to return to baseline PRU=-3.350+0.079\*PI(1)+0.014\*baseline PRU. The predicted number of days to return to baseline based on device-derived platelet percentage inhibition is reported for each treatment group.
Time frame: up to 12 days after the last dose
Population: Participants in the Primary Population. The Primary Population included participants who entered the Washout Period and had platelet function testing data at both baseline (Visit 2) and Washout Period Day 1 (Visit 3). The primary definition of return to baseline was (Baseline PRU-PRU) less than or equal to 60 units.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Time to Return to Baseline PRU for the Primary Population Using the Primary Definition of Return to Baseline in Relation to the Inhibition of Platelet Aggregation 24 Hours Following the Last Maintenance Dose | 6.2 days |
| Clopidogrel | Time to Return to Baseline PRU for the Primary Population Using the Primary Definition of Return to Baseline in Relation to the Inhibition of Platelet Aggregation 24 Hours Following the Last Maintenance Dose | 3.7 days |