| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects with symptoms of Coronary Heart Disease |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to evaluate the safety of SCH 530348 with respect to the incidence of major and minor bleeding events, as assessed by the TIMI (Thrombolysis in Myocardial Infarction cooperative group) system of classification, in addition to the standard of care in subjects undergoing non-urgent PCI, and as maintenance therapy after the procedure. |
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| E.2.2 | Secondary objectives of the trial |
1. incidence/tolerability of bleeding not meeting the TIMI major or minor criteria;
2. incidence of "clinically important" bleeding occurring after discharge;
3. inhibition of platelet aggregation induced by various agonists as an indicator of the desired pharmacodynamic effect;
4. incidence of the composite endpoint of death and major adverse cardiac events (MACE: non-fatal MI, ischemia requiring rehospitalization, or coronary revascularization with CABG or PCI) in addition to standard of care and as maintenance therapy as a measure of clinical benefit;
5. incidence of the individual components of the death/MACE composite, as well as other composites such as (a) cardiovascular death and nonfatal MI, (b) cardiovascular death and stroke, and (c) cardiovascular death, nonfatal MI, and stroke as measures of clinical benefit and
6. effect on expression of markers of inflammation and of platelet release and activation (ie, hs-CRP, CD40 ligand [CD40L], and membrane-bound P-selectin).
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Subjects must meet all the following:
1. man or woman of any race/ethnicity greater than or equal to 55 years who has had symptoms of CAD;
2. scheduled to undergo non-urgent PCI, or non-urgent cardiac catheterization with the intent to undergo PCI;
3. no anticipation that the subject would require treatment with a GP IIb/IIIa inhibitor prior to initiation of intervention if the subject were not a participant in the current trial, and no anticipation of use during this trial;
4. willing to give appropriate informed consent and complete all study-related procedures, and able to adhere to dosing and visit schedules; and
5. women of child-bearing potential (all postmenarchal women who are <2 years menopausal or who have not had surgical sterilization or a hysterectomy are considered to be women of child-bearing potential) must agree to use a medically accepted method of contraception while receiving protocol-specified medication, and for 60 days after stopping the medication.
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| E.4 | Principal exclusion criteria |
Subject will be excluded if one of the following are met:
1. pregnancy (premenopausal women should have a negative pregnancy test result confirmed before enrollment);
2. ongoing chest pain (or anginal equivalent) leading to urgent referral for PCI, or ongoing chest pain (or anginal equivalent) at the time of study enrollment;
3. history of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before enrollment;
4. stroke or transient ischemic attack (TIA) of any cause or origin within 30 days before enrollment, or history of a hemorrhagic stroke at any time;
5. severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) while receiving therapy;
6. known platelet count <150,000/mm3;
7. uncontrolled cardiac arrhythmia;
8. known impairment of renal function (serum creatinine >2.0 mg/dL [>176.8 micromol/L]), dysproteinemia, nephrotic syndrome, or other renal disease (24-hour urinary protein greater than or equal to 3+ or greater than or equal to 1 g);
9. active or chronic hepatobiliary or hepatic disease, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activity more than three times greater than the upper limit of the laboratory reference range;
10. major surgery within 6 weeks before enrollment;
11. concurrent treatment with a Factor Xa inhibitor;
12. anticipated subsequent staged multivessel PCI procedure within a period of 30 days after enrollment;
13. concurrent or anticipated treatment with warfarin after enrollment;
14. treatment with any parenteral GP IIb/IIIa inhibitor within the previous 30 days before enrollment, or concurrent treatment with any other antiplatelet agent other than aspirin and clopidogrel, or with any other PAR 1 inhibitor;
15. anticipated intracoronary brachytherapy;
16. serious illness/condition that the investigator feels would interfere with the study evaluations or participation in the studyor pose a hazard to the subject;
17. known hypersensitivity to any component of the IMP;
18. participation in a study of experimental therapy or use of any investigational drug within 30 days of enrollment;
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The incidence of TIMI major plus minor bleeding in the primary evaluable cohort (those undergoing PCI) through the end of treatment. TIMI Major bleeding will be defined as (1) intracranial hemorrhage or (2) clinically significant overt signs of bleeding associated with a decrease in hemoglobin concentration of >5 g/dL (or hematocrit >15%). TIMI Minor bleeding will be defined as clinically overt signs of bleeding associated with a decrease in hemoglobin concentration of 3 to less than or equal to 5 g/dL (hematocrit 9% to less than or equal to 15%) that does not otherwise meet criteria for major bleeding. Hemoglobin concentration and hematocrit will be adjusted for any transfusion of packed red blood cells or whole blood given between enrollment and post-transfusion measurements by the method of Landefeld and coworkers. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Sequential escalating dose |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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