Prasugrel/Clopidogrel Maintenance Dose Washout Study

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01014624
• Collaborator: (none)
• Enrollment: 56
• Locations: 4
• Arms: 2
• Actual Duration (Months): 3.9
• Patients Per Site: 14
• Patients Per Site Per Month: 3.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Prasugrel; Drug: Clopidogrel	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Recovery of Platelet Function Following Discontinuation of Prasugrel or Clopidogrel Maintenance Dosing in Aspirin-Treated Subjects With Stable Coronary Disease
• Actual Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prasugrel Prasugrel 10mg administered for 7 days followed by a Washout Period up to 12 days.	Drug: Prasugrel; 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.; Other Names: Effient
Active Comparator: Clopidogrel Clopidogrel 75mg administered for 7 days followed by a 12 day Washout Period up to 12 days.	Drug: Clopidogrel; 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.; Other Names: Plavix

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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%.

2. 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%.

3. 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%.

4. 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%.

5. 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%.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts 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 Exclusion Criteria:

• Any known contraindication to treatment with an anticoagulant or antiplatelet agent

• Prior history or clinical suspicion of cerebral vascular malformations, intracranial tumor, transient ischemic attack (TIA), or stroke, or recent history (within 3 months) of head trauma

• Prior history or presence of significant bleeding disorders (eg, hematemesis, melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intraocular bleeding)

• History (within the last 5 years) or presence of gastric ulcers. Previous history of duodenal ulcer is acceptable but must have been successfully surgically or medically treated with no further evidence of disease in the past 6 months (from screening).

• Prior history of abnormal bleeding tendency (ie, prolonged bleeding on dental extraction, tonsillectomy, or previous surgical procedure)

• Known prior history of thrombocytopenia (platelet count < 100,000/mm³) or thrombocytosis (platelet count > 500,000/mm³) or recent history (within six months) of hemoglobin < 10 mg/dL

• Clinically significant out of range values for prothrombin time, activated partial thromboplastin time (aPTT), platelet count, or hemoglobin at screening, in the investigator's opinion

• History of major surgery, severe trauma, fracture, or organ biopsy within 3 months prior to enrollment

• Prior/Concomitant Therapy Exclusion Criteria:

• Subjects taking prasugrel, clopidogrel, ticlopidine, cilostazol, dipyridamole, warfarin, heparin, direct thrombin inhibitors, or glycoprotein IIB/IIIa inhibitors =10 days prior to screening or during study participation

• The use (or planned use) of fibrinolytic agents within 30 days before screening or during study participation

• Subjects receiving treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors exceeding 3 doses per week

• Subjects receiving proton pump inhibitors (PPIs), eg, (lansoprazole, esomeprazole, omeprazole, pantoprazole, or rabeprazole) =10 days prior to screening or during study participation

• General Exclusion Criteria:

• Investigator site personnel directly affiliated with the study or immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted

• Daiichi Sankyo or Eli Lilly employees

• Currently enrolled in, or discontinued within the last 30 days prior to baseline from, a clinical study involving an off-label use of an investigational drug or device, or concurrently enrolled in a non-observational clinical study or any other type of medical research judged not to be scientifically or medically compatible with this study

• Have previously completed or withdrawn from this study

• Women who are known to be pregnant and/or who receive a positive serum pregnancy test result, who have given birth within the past 90 days, and/or who are breastfeeding

• Results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the subject, as determined by the investigator

• Known allergies or intolerance to aspirin and/or thienopyridines (prasugrel, clopidogrel, or ticlopidine)

• Evidence of significant active neuropsychiatric disease, alcohol abuse or drug abuse, in the investigator's opinion

• Evidence of active hepatic disease, or any of the following; positive human immunodeficiency virus (HIV) antibodies, positive hepatitis C antibody, positive hepatitis B surface antigen; serum alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyltransferase (GGT) >/= 3 times the upper limit of normal (ULN) laboratory reference range; or bilirubin >/= 2 times the ULN of laboratory reference range at screening

• Subjects who are unreliable and unwilling to make themselves available for the duration of the study and who will not abide by the research unit policy and procedure and study restrictions

• Subjects who have had an angiogram </= 7 days before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scripps Clinic	La Jolla	California	United States	92037
2	University of Florida Health Science Center Shands Jacksonville	Jacksonville	Florida	United States	32209
3	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio	United States	45212
4	Black Hills Clinical Research Center	Rapid City	South Dakota	United States	57701

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01014624
• Other Study ID Numbers: CS747S-B-U4001
• First Posted: Nov 17, 2009
• Last Update Posted: Jun 28, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Daiichi Sankyo, Inc.: thienopyridine; pharmacologic action; prasugrel; clopidogrel
• Additional relevant MeSH terms: Coronary Artery Disease; Clopidogrel; Prasugrel Hydrochloride

Study Results

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 Detail	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).

Arm/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Period Title: Overall Study
STARTED	29	27
COMPLETED	27	26
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Prasugrel	Clopidogrel	Total
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.	Total of all reporting groups
Overall Participants	29	27	56
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.5 (8.45)	62.3 (8.10)	59.80 (8.56)
Sex: Female, Male (Count of Participants)
Female	4 13.8%	7 25.9%	11 19.6%
Male	25 86.2%	20 74.1%	45 80.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.4%	0 0%	1 1.8%
Not Hispanic or Latino	28 96.6%	27 100%	55 98.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.4%	0 0%	1 1.8%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 17.2%	5 18.5%	10 17.9%
White	22 75.9%	22 81.5%	44 78.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.4%	0 0%	1 1.8%
weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	97.3 (15.13)	90.8 (14.41)	94.1 (15.02)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	174.1 (8.20)	173.5 (9.00)	173.8 (8.52)
Ethnicity (participants) [Number]
Hispanic or Latino	1 (0) 3.4%	0 (0) 0%	1 (0) 1.8%
Non Hispanic or Latino	28 (0) 96.6%	27 (0) 100%	55 (0) 98.2%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.0 (4.07)	30.3 (5.34)	31.2 (4.76)
Smoking Status (participants) [Number]
Never smoked	7 (0) 24.1%	10 (0) 37%	17 (0) 30.4%
Currently Smoke	10 (0) 34.5%	6 (0) 22.2%	16 (0) 28.6%
Formerly Smoked	12 (0) 41.4%	11 (0) 40.7%	23 (0) 41.1%
Alcohol Use (participants) [Number]
Never used alcohol	3 (0) 10.3%	5 (0) 18.5%	8 (0) 14.3%
Currently use alcohol	19 (0) 65.5%	18 (0) 66.7%	37 (0) 66.1%
Formerly used alcohol	7 (0) 24.1%	4 (0) 14.8%	11 (0) 19.6%
Diabetes status (participants) [Number]
Does not have diabetes	18 (0) 62.1%	16 (0) 59.3%	34 (0) 60.7%
Has diabetes	11 (0) 37.9%	11 (0) 40.7%	22 (0) 39.3%

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout period up to 12 days.
Measure Participants	28	26
return to baseline PRU by washout day 1	0 0%	30.8 114.1%
return to baseline PRU by washout day 3	3.6 12.4%	53.9 199.6%
return to baseline PRU by washout day 5	37.0 127.6%	84.6 313.3%
return to baseline PRU by washout day 6	62.9 216.9%	96.2 356.3%
return to baseline PRU by washout day 7	77.8 268.3%	96.2 356.3%
return to baseline PRU by washout day 9	100.0 344.8%	100.0 370.4%

2. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	26
returned to baseline PRU by washout day 1	0.0 0%	30.8 114.1%
returned to baseline PRU by washout day 3	0.0 0%	53.9 199.6%
returned to baseline PRU by washout day 5	37.0 127.6%	80.8 299.3%
returned to baseline PRU by washout day 6	55.6 191.7%	88.5 327.8%
returned to baseline PRU by washout day 7	77.8 268.3%	96.2 356.3%
returned to baseline PRU by washout day 9	100.0 344.8%	100.0 370.4%

3. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	26
Washout day 50% returned to baseline PRU	6	3
Washout day 75% returned to baseline PRU	7	5
Washout day 90% returned to baseline PRU	9	6

4. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	26
Washout day 50% returned to baseline PRU	6	3
Washout day 75% returned to baseline PRU	7	5
Washout day 90% returned to baseline PRU	9	7

5. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	15
Washout day 50% returned to baseline PRU	6	5
Washout day 75% returned to baseline PRU	7	5
Washout day 90% returned to baseline PRU	9	6

6. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	15
Washout day 50% returned to baseline PRU	6	5
Washout day 75% returned to baseline PRU	7	6
Washout day 90% returned to baseline PRU	9	7

7. Secondary Outcome

Title	Percentage of Inhibition of Platelet Aggregation on Washout Day 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	26
Mean (Standard Deviation) [percentage]	72.3 (11.78)	35.4 (23.35)

8. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.	Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
Measure Participants	28	26
Number [days]	6.2	3.7

Adverse Events

Time Frame	Beginning with screening, adverse events (AEs) were assessed at every visit. All AEs occuring after participant signed informed consent and up to 14 days after last dose of study drug were recorded
Arm/Group Title	Prasugrel		Clopidogrel
Arm/Group Description	Prasugrel 10mg tablet administered once daily for 7 days followed by a Washout Period up to 12 days.		Clopidogrel 75 mg tablet administered once daily for 7 days followed by Washout Period up to 12 days.
All Cause Mortality
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/29 (41.4%)		9/27 (33.3%)
Ear and labyrinth disorders
eyelid oedema	1/29 (3.4%)	1	0/27 (0%)	0
Gastrointestinal disorders
Adominal discomfort	1/29 (3.4%)	1	0/27 (0%)	0
Diarrhoea	1/29 (3.4%)	1	2/27 (7.4%)	2
Nausea	0/29 (0%)	0	1/27 (3.7%)	1
Adominal pain upper	0/29 (0%)	0	1/27 (3.7%)	1
General disorders
Pain	1/29 (3.4%)	1	0/27 (0%)	0
Infections and infestations
nasopharyngitis	0/29 (0%)	0	1/27 (3.7%)	1
Upper respiratory tract infection	0/29 (0%)	0	1/27 (3.7%)	1
viral infection	1/29 (3.4%)	1	0/27 (0%)	0
Metabolism and nutrition disorders
diabetes mellitus	0/29 (0%)	0	1/27 (3.7%)	1
Nervous system disorders
dizziness	1/29 (3.4%)	1	0/27 (0%)	0
headache	1/29 (3.4%)	1	0/27 (0%)	0
Psychiatric disorders
insomnia	1/29 (3.4%)	1	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
epistaxis	2/29 (6.9%)	2	0/27 (0%)	0
Skin and subcutaneous tissue disorders
ecchymosis	0/29 (0%)	0	1/27 (3.7%)	1
increased tendency to bruise	2/29 (6.9%)	2	0/27 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.