A Pharmacokinetic and Pharmacodynamic Comparison of Prasugrel (LY640315) versus Clopidogrel in Subjects with Stable Atherosclerosis - TABR

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005292-15-SE
• Date of registration: 18/01/2006
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Ltd.
• Public title: A Pharmacokinetic and Pharmacodynamic Comparison of Prasugrel (LY640315) versus Clopidogrel in Subjects with Stable Atherosclerosis - TABR
• Scientific title: A Pharmacokinetic and Pharmacodynamic Comparison of Prasugrel (LY640315) versus Clopidogrel in Subjects with Stable Atherosclerosis - TABR
• Date of first enrolment: 02/03/2006
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005292-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male or female subjects with a history of stable coronary artery disease in whom co-administration of aspirin and a thienopyridine (i.e., clopidogrel or ticlopidine) is not contraindicated.
Coronary artery disease is defined as any of the following: Subjects diagnosed with chronic stable angina; prior history of unstable angina (including non-ST-segment elevation myocardial infarction) or acute myocardial infarction (AMI); previous coronary revascularization including percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG); or CAD in at least one coronary vessel on previous angiography or noninvasive imaging procedure.
2.Subjects between the ages of 40 and 75 years (inclusive) with a competent mental condition to provide written informed consent before entering the study. Subjects must provide written informed consent approved by Eli Lilly and Company and the Ethical Review Board governing each site.
3.Women who are not of child-bearing potential; in other words, either post-menopausal and/or surgical sterilization (including tubal ligation). Post menopausal females are defined as at least 2 years post cessation of menses.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Cardiovascular Exclusion Criteria
1.Subjects with unstable coronary artery disease, defined as any of the following observed at screening: new, increased, or rest angina; hospitalization for unstable angina within the previous 30 days; diagnosis of MI within previous 30 days; PCI within previous 90 days; or CABG within previous 90 days.
2.Subjects with a history of refractory ventricular arrhythmias.
3.Subjects with a history of an implantable defibrillator device.
4.Subjects with a history or evidence of congestive heart failure (NYHA Class III or above) within 6 months prior to screening.
5.Subjects with significant hypertension (systolic blood pressure >180 or diastolic blood pressure >110 mmHg) at the time of screening or randomization.
6.Any coronary revascularization (surgical or percutaneous) performed within 3 months prior to randomization.
7.Any coronary revascularization (surgical or percutaneous) planned within 40 days following randomization.
Bleeding Risk Exclusion Criteria
8.Any known contraindication to treatment with an anticoagulant or antiplatelet agent.
9.Prior history or presence of significant bleeding disorders (for example, hematemesis, melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intraocular bleeding).
10.Prior history or clinical suspicion of cerebral vascular malformations, for example, prior history of cerebral hemorrhage, aneurysm or premature stroke (CVA <65 years of age).
11.Prior history of abnormal bleeding tendency (i.e. prolonged bleeding on dental extraction, tonsillectomy, or previous surgical procedure).
12.Personal or family history of coagulation or bleeding disorders.
13.Prior history of thrombocytopenia (platelet count < 100,000/mm3) or thrombocytosis (platelet count > 500,000/mm3).
14.Clinically significant out of range values for PT, aPTT, platelet count or hemoglobin at screening, in the investigator’s opinion.
15.History of major surgery, severe trauma, fracture or organ biopsy within 3 months prior to enrollment.
16.Any planned surgical procedure within 40 days following randomization.
Prior/Concomitant Therapy Exclusion Criteria
17.Subjects taking ticlopidine or clopidogrel less than or equal 10 days prior to screening.
18.The use (or planned use) of antiplatelet agents (besides aspirin), heparin, warfarin or fibrinolytic agents within 30 days of screening.
19.Subjects 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.
General Exclusion Criteria
20.Women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding.
21.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.
22.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.
23.Subjects enrolled in either another investigational drug study, in another investigational device study, or in another investigational study of an approved drug within 30 days prior to Visit 1 of the current study.
24.Known allergies or intolerance to aspirin and/or thienopyridines (clopidogrel, prasugrel or ticlopidine).
25.Evidence of significant active neuropsychiatric disease, alcohol abuse or drug abuse, in the investigator’s opi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stable atherosclerosis
MedDRA version: 7.0 Level: HLT Classification code 10011085

Intervention(s)

Product Name: Prasugrel
Product Code: CS-747, LY640315
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: prasugrel
CAS Number: 389574-19-0
Current Sponsor code: CS-747 hydrochloride salt, LY640315
Other descriptive name: LY640315
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 10-60
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Plavix
Product Name: Plavix
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: clopidogrel
CAS Number: 113665-84-2
Other descriptive name: Clopidogrel hydrogen sulphate
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 75-600
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: •Assess pharmacodynamic effects of prasugrel after 60mg LD+aspirin vs clopidogrel 600mg LD+aspirin
•Assess pharmacodynamics effects of 10mg daily MD prasugrel+aspirin vs 75mg daily MD clopidogrel+aspirin
•Compare rate of nonresponders for prasugrel vs clopidogrel
•Compare pharmacokinetic profile of active metabolites for LD and daily MD prasugrel and clopidogrel
•Assess safety/tolerability for prasugrel vs clopidogrel when co-administered with aspirin in subjects with stable atherosclerosis
•Assess vasodilator-associated stimulated of platelet activation and other flow cytometric biomarkers of platelet activation of prasugrel vs clopidogrel co-administered with aspirin
•Assess levels ADP-induced IPA using light transmission aggregometry compared with a point-of-care monitoring device for IPA
•Assess if variable IPA observed with clopidogrel reflects P2Y12 ADP receptor heterogeneity by the active metabolite of clopidogrel

Primary end point(s): The primary endpoint of the study is the mean change from baseline (pre-LD) in MPA to 20 µM ADP at 2 hours post-LD .

Main Objective: The primary objective of this study is to compare the pharmacodynamic effect of a prasugrel 60 mg Loading Dose with a clopidogrel 600 mg Loading Dose, as assessed by change in mean maximal platelet aggregation to 20 mM ADP at 2 hours after LD administration, in aspirin-treated subjects with stable atherosclerosis.

Secondary ID(s)

H7T-MC-TABR & TABR (1)