Comparison of Prasugrel and Clopidogrel in Very Elderly a... | NCT01107912

ID	Type	Description	Link
H7T-MC-TACY	Other Identifier	Eli Lilly and Company

Name	Class
Daiichi Sankyo Co., Ltd.	INDUSTRY

Label	Type	Intervention Names
5 milligrams (mg) prasugrel	Experimental	Drug: prasugrel
10 mg prasugrel	Active Comparator	Drug: prasugrel
75 mg clopidogrel	Active Comparator	Drug: clopidogrel

Name	Type	Description	Arm Group Labels	Other Names
prasugrel	Drug	administered orally, daily for 12 days	10 mg prasugrel 5 milligrams (mg) prasugrel

Measure	Description	Time Frame
Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period	Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). Lower MPA values reflect stronger platelet inhibition, whereas higher MPA values reflect weaker inhibition.	Baseline, 12 days

Measure	Description	Time Frame
Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy	Vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12, whereas a higher PRI reflects weaker inhibition of P2Y12.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants (Either: at least 45 years of age, but less than 65 years of age OR 75 years of age or older) with a history of stable coronary artery disease who are not currently indicated for treatment with a thienopyridine (that is, prasugrel, clopidogrel, or ticlopidine)
Provision of written informed consent
Body weight greater than or equal to 60 kilograms (kg)
For women of child-bearing potential only (that is, women who are not surgically or chemically sterilised and who are between menarche and 1 year post menopause), test negative for pregnancy (based on a urine or serum pregnancy test to be performed before randomisation) and agree to use a reliable method of birth control during the study

Exclusion Criteria:

Unstable coronary artery disease
Myocardial Infarction (MI) within the previous 30 days
Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft Surgery (CABG) within the previous 90 days
History of refractory ventricular arrhythmias within the last 6 months; an implanted defibrillator device; congestive heart failure within 6 months prior to screening; major surgery, or severe trauma, fracture or organ biopsy within 3 months prior to enrollment
Any planned surgical procedure or any coronary revascularisation (surgical or percutaneous) planned within 60 days following randomisation
Any known contraindication to treatment with an antiplatelet agent
Significant hypertension at the time of screening or randomisation
Clinically significant out-of-range values for platelet count or haemoglobin at screening, in the investigator's opinion, or results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the study population, as determined by the investigator
Prior history or presence of significant bleeding disorders, abnormal bleeding tendency, or personal history of coagulation or bleeding disorders
Prior history or clinical suspicion of cerebral vascular malformations, intracranial neoplasm, Transient Ischemic Attack (TIA) or stroke
Prior history of thrombocytopenia or thrombocytosis
Use of antiplatelet agents (besides aspirin) within 10 days prior to screening; the use (or planned use) of heparin, oral anticoagulants, or fibrinolytic agents within 30 days of screening; or participants receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Jacksonville	Florida	32209

PubMed Identifier	Type	Citation	Retractions
23747759	Derived	Erlinge D, Gurbel PA, James S, Lindahl TL, Svensson P, Ten Berg JM, Foley DP, Wagner H, Brown PB, Luo J, Zhou C, Moser BA, Jakubowski JA, Small DS, Winters KJ, Angiolillo DJ. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol. 2013 Aug 13;62(7):577-83. doi: 10.1016/j.jacc.2013.05.023. Epub 2013 Jun 7.

ID	Title	Description
FG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.
FG001	10 mg Prasugrel (Elderly)

ID	Title	Description
BG000	Very Elderly, Drug Sequence ABC	Participants (≥75 years of age) in this arm received study drug sequence ABC. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg.
BG001	Very Elderly; Drug Sequence ACB	Participants (≥75 years of age) in this arm received study drug sequence ACB. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg.
BG002	Non-Elderly; Drug Sequence BAC	Participants (≥45 to <65 years of age) in this arm received study drug sequence BAC. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg.
BG003	Non-Elderly; Drug Sequence BCA	Participants (≥45 to <65 years of age) in this arm received study drug sequence BCA. A = Prasugrel 5mg, B = Prasugrel 10mg, C = Clopidogrel 75mg.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00036 BG00137 BG00242 BG00340 BG004155

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

Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period

Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). Lower MPA values reflect stronger platelet inhibition, whereas higher MPA values reflect weaker inhibition.

All randomized participants who continued in the study through the Day 12 visit, and who had at least 1 evaluable PD assessment at the Day 12 visit. Participants were analysed based on randomized treatment assignment, regardless of the study drug they took.

Posted

Median

Inter-Quartile Range

percentage of aggregation

Baseline, 12 days

ID	Title	Description
OG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.
OG001	10 mg Prasugrel (Non-Elderly)	Non-elderly participants (≥45 to <65 years of age) received 10 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 5 mg prasugrel or 75 mg clopidogrel dose in Period 2.

Units	Counts
Participants	OG00072 OG00179

Title

Denominators

Categories

Baseline

Title	Measurements
	OG00078.00(72.00 to 83.50) OG00175.00(71.00 to 83.00)

Period 1 (12 days) (n=71, 79)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Estimate of the difference	6.00			2-Sided	95	1.00	9.00				Yes	Non-Inferiority or Equivalence	The difference of median MPA to 20 μM ADP of a prasugrel 5-mg in the elderly group to the 75th percentile of the MPA to 20 μM ADP of a prasugrel 10 mg MD in the non-elderly group at the end of Period 1 was estimated from the observed data. The upper limit of the one-sided 97.5% confidence interval for the difference was estimated from resampling data with replacement through bootstrap methodology and was used to compare with the non-inferiority margin of 15 percentage points.

Secondary

Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy

Vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12, whereas a higher PRI reflects weaker inhibition of P2Y12.

All randomized participants who received at least 1 dose of study drug and provided at least 1 evaluable pharmacodynamic (PD) measure at 1 of the 3 periods. Participants were analyzed based on the treatment they received for each period regardless of their randomized treatment assignment.

Posted

Mean

Standard Deviation

percentage platelet reactive index (PRI)

Baseline, Day 12

ID	Title	Description
OG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.
OG001	10 mg Prasugrel (Elderly)	Elderly participants ( ≥75 year of age) on 5 mg prasugrel in Period 1 who received 10 mg prasugrel during Period 2 or 3.
OG002	75 mg Clopidogrel (Elderly)

Secondary

Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy

The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in P2Y12 reaction units (PRU). PRU report the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of the rate and extent of platelet aggregation in the presence of adenosine phosphate ADP. A lower PRU reflects stronger inhibition of P2Y12, whereas a higher PRU reflects weaker inhibition of P2Y12.

Posted

Mean

Standard Deviation

P2Y12 reaction units (PRU)

Baseline, Day 12

ID	Title	Description
OG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.
OG001	10 mg Prasugrel (Elderly)	Elderly participants ( ≥75 year of age) on 5 mg prasugrel in Period 1 who received 10 mg prasugrel during Period 2 or 3.
OG002

Secondary

Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing

A descriptive pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing prasugrel and clopidogrel active metabolite exposures to MPA in response to 20 µM ADP (by LTA) was conducted as originally intended; however, the graphic output from that analysis is not possible here. Therefore, the PK portion is presented here as AUC and the PD portion is presented in Secondary Outcome Measure #5. AUC was calculated through the last scheduled sampling time of 4 hours [AUC (0-4)] or through the sampling time of the last quantifiable concentration prior to 4 hours. AUC values were denoted AUC(0-tlast) in both instances.

All available PK sample data from all treated participants who contributed complete PK profiles.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram*hour/milliliter (ng*hr/mL)

Baseline up to 4 hours post-dose

Participant PK Profiles

Participants

ID	Title	Description
OG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.
OG001	10 mg Prasugrel (Elderly)	Elderly participants ( ≥75 year of age) on 5 mg prasugrel in Period 1 who received 10 mg prasugrel during Period 2 or 3.

Secondary

Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy

Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.

Posted

Mean

Standard Deviation

percentage of aggregation

Baseline, Day 12

ID	Title	Description
OG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.
OG001	10 mg Prasugrel (Elderly)	Elderly participants ( ≥75 year of age) on 5 mg prasugrel in Period 1 who received 10 mg prasugrel during Period 2 or 3.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0021 events1 affected72 at risk EG0030 events0 affected79 at risk EG0040 events0 affected82 at risk EG0050 events0 affected79 at risk
Haemorrhagic diathesis	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Palpitations	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Eye haemorrhage	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Ocular hypertension	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Faeces discoloured	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected71 at risk EG0020 events0 affected72 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected71 at risk EG0021 events1 affected72 at risk EG003
Chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected71 at risk EG0022 events2 affected72 at risk EG003
Inflammation	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Infusion site haemorrhage	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Oedema peripheral	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Pyrexia	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Hepatic cyst	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0006 events5 affected73 at risk EG00112 events9 affected71 at risk EG0029 events4 affected72 at risk EG003
Ear abrasion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Periorbital haematoma	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Traumatic haematoma	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0022 events1 affected72 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Bleeding time prolonged	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Blood creatinine	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Blood potassium decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Blood urea	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Blood urine present	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events1 affected71 at risk EG0021 events1 affected72 at risk EG003
Cardiac enzymes increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Eosinophil count increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0021 events1 affected72 at risk EG003
Haematocrit decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Burning sensation	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0021 events1 affected72 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0013 events2 affected71 at risk EG0021 events1 affected72 at risk EG003
Migraine	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Presyncope	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Sciatica	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0014 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected73 at risk EG0016 events3 affected71 at risk EG0021 events1 affected72 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0023 events1 affected72 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Skin haemorrhage	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Haematoma	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG00110 events9 affected71 at risk EG0024 events2 affected72 at risk EG003
Hypertension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003

ID	Term
D003327	Coronary Disease
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D014652	Vascular Diseases

ID	Term
D013876	Thiophenes
D013457	Sulfur Compounds
D009930	Organic Chemicals
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D013988	Ticlopidine
D058924	Thienopyridines
D011725	Pyridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	5 mg Prasugrel (Elderly)	Elderly participants (≥75 Years of Age) received 5 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 10 mg prasugrel or 75 mg clopidogrel dose in Period 2.	0	73	20	73
EG001	10 mg Prasugrel (Elderly)	Elderly participants ( ≥75 year of age) on 5 mg prasugrel in Period 1 who received 10 mg prasugrel during Period 2 or 3.	2	71	31	71
EG002	75 mg Clopidogrel (Elderly)	Elderly participants (≥75 year of age) on 5 mg prasugrel in Period 1 who received 75 mg clopidogrel during Period 2 or 3.	2	72	25	72
EG003	5 mg Prasugrel (Non-Elderly)	Non-elderly participants (≥45 to <65 years of age) on 10 mg prasugrel in Period 1 who received 5 mg prasugrel during Period 2 or 3.	0	79	23	79
EG004	10 mg Prasugrel (Non-Elderly)	Non-elderly participants (≥45 to <65 years of age) received 10 mg prasugrel for 12 days during Period 1 without intervening or terminal washout periods. They were then switched to either the 5 mg prasugrel or 75 mg clopidogrel dose in Period 2.	2	82	39	82
EG005	75 mg Clopidogrel (Non-Elderly)	Non-elderly participants ( ≥45 to <65 years of age) on 10 mg prasugrel during Period 1 who received 75 mg clopidogrel during Period 2 or 3.	0	79	23	79

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Eosinophilia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG0030 events0 affected79 at risk EG0040 events0 affected82 at risk EG0050 events0 affected79 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0021 events1 affected72 at risk EG003
Endocarditis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected71 at risk EG0020 events0 affected72 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected71 at risk EG0020 events0 affected72 at risk EG003