| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10051592 |
| E.1.2 | Term | Acute coronary syndrome |
|
| 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 hypothesis that SCH 530348 added to standard of care will reduce the incidence of atherothrombotic ischemic events relative to standard of care alone, as measured by the composite of cardiovascular (CV) death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization (revasc). |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary obj: evaluate benefit with respect to the composite of CV death, MI, and stroke.
Other secondary efficacy obj: eval incidence of:
1. CV death, MI , stroke, and urgent coronary revasc
2. CV death and MI
3. all-cause death, MI, stroke, recurrent ischemia with rehospitalization, and urgent coronary revasc
4. all-cause death, MI, stroke and urgent coronary revasc
5. individual components of composite primary efficacy endpt: CV death, MI, stroke, recurrent ischemia with rehospitalization, urgent coronary revasc
6. all-cause death.
Safety obj: eval incidence of:
1. composite of moderate and severe bleeding events according to GUSTO
2. "clinically significant bleeding" defined as TIMI major or TIMI minor bleeding, or bleeding that requires unplanned medical or surgical treatment, or lab eval even if it does not meet criteria for TIMI major or TIMI minor bleeding |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The subject must meet ALL the criteria listed below for entry:
1. Subject must be 18 years of age or older, and may be of either sex and of any race
2. Subject must have a current clinical manifestation of NSTEACS according to the following 3 criteria:
a. history of cardiac-ischemia-related symptoms of at least 10 minutes duration ≤24 hours prior to hospital presentation
AND
b. any one (or more) of the following 2 criteria:
i. concurrent biomarker evidence - elevated troponin I or troponin T greater than the
stated upper limit of normal (ULN) at the study site, OR creatine kinase-myocardial band (CK-MB) greater than the ULN at the study site
ii. concurrent electrocardiographic evidence - electrocardiogram (ECG) changes comprising new or presumably new ST-segment depression ≥0,1 mV (≥ 1 mm), or transient (<30 minutes) ST-segment elevation ≥0,1 mV (≥ 1 mm) in at least two contiguous leads
AND
c. any one (or more) of the following criteria:
i. age ≥ 55 years (Note: Subjects 55 to 59 years will be enrolled so long as the overall occurrence of blinded suspected endpoint events in this age group remains at least a minimum acceptable level as determined by the Executive Committee. Should the occurrence in this age group decrease below a minimum acceptable level as determined by the Executive Committee, the committee may recommend to the sponsor that this age category be removed as a sufficient third criterion for eligibility. Should the sponsor accept the recommendation, investigators would be notified that, moving forward, only age ≥ 60 years would be a sufficient third criterion for eligibility).
ii. documented prior history of MI or coronary revascularization (PCI or CABG)
iii. diabetes [documented use of insulin or oral hypoglycemic(s)]
iv. peripheral arterial disease as indicated by a history of intermittent claudication and either
a. a resting ankle/brachial index of<0.85, or
b. amputation, peripheral bypass, or peripheral angioplasty of the extremities
secondary to ischemia
3. Subject must be willing and able to give informed consent
4. A woman of child-bearing potential who is currently sexually active must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 2 months after stopping the medication. Highly effective methods of birth control are defined as those that result in a low failure rate (ie, <1% per year) when used consistently and correctly, such as hormonal implants, injectables, combined oral contraceptives, hormonal intrauterine devices, sexual abstinence, or surgical sterilization (eg, vasectomy of male partner).
5. A woman of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study.
|
|
| E.4 | Principal exclusion criteria |
The subject will be excluded from entry if ANY of the criteria listed below are met:
1. Concurrent or anticipated treatment with warfarin (or derivatives, eg, phenprocoumon), oral factor Xa inhibitor, or oral direct thrombin inhibitor after enrollment. (Note 1: If a subject is taking warfarin during determination of eligibility and the investigator is willing to stop the subject’s treatment with warfarin immediately, and the subject is not otherwise disqualified from participation, then the subject may receive randomized assignment of the study drug). (Note 2: A subject who was not using warfarin/derivatives and for whom use was not anticipated, but who subsequently requires warfarin/derivatives after randomized assignment of study drug may continue treatment with warfarin/derivatives and randomized study drug, except when aspirin/thienopyridine/warfarin concurrent therapy is needed and thienopyridine cannot be discontinued).
2. Concurrent or anticipated treatment with a potent inducer (eg, rifampin) or potent inhibitor (eg, ketoconazole, erythromycin) of CYP3A4 isoenzymes (detailed list will be supplied to investigator). (Note: A subject who was not using a potent CYP 3A4 inducer or potent inhibitor and/or for whom such therapy was not anticipated, but who subsequently requires such therapy after randomization may receive such therapy as follows:
a. potent 3A4 inducer – continue study drug until therapy with inducer ends or until
inducer therapy extends beyond 4 weeks, then discontinue study drug.
b. potent 3A4 inhibitor – interrupt study drug until inhibitor therapy ends or until
inhibitor therapy extends beyond 4 weeks, then discontinue study drug).
3. History of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before enrollment
4. History at any time of intracranial hemorrhage (except “microhemorrhage”), intracranial or spinal cord surgery, or a central nervous system tumor or aneurysm
5. Documented sustained severe hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg) at enrollment or within the previous 10 days
6. Severe valvular heart disease, as defined by the American College of Cardiology/American Heart Association
7. History within 2 weeks prior to enrollment of major surgery other than mentioned above or of ischemic (presumed thrombotic) stroke
8. Known history of thrombocytopenia (conventionally defined as platelet count <100,000/mm3) occurring within 30 days before enrollment
9. Known hepatobiliary disease, or known unexplained persistent increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) activity to two times or more the upper limit of the reference range (upper limit of normal [≥2xULN]) within 30 days before enrollment
10. Any serious illness or any condition that the investigator feels would (a) pose a significant hazard to the subject if investigational therapy were initiated, or (b) would limit the prognosis of the subject, regardless of investigational therapy
11. Any serious medical comorbidity (eg, active malignancy) such that the subject's life expectancy is < 24 months
12. Previous participation in the current study
13. Current participation in any other study of investigational therapy, or participation in such a study within the last 30 days
14. Known hypersensitivity to any component of the current investigational product
15. Subject is a woman who is breast-feeding, pregnant or who intends to become pregnant (affirm that a female subject of child-bearing potential is not pregnant before enrollment).
16. Subject is part of the staff personnel directly involved with this study, or is a family member of the investigational staff
17. Known current substance abuse at the time of enrollment
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the first occurrence of any component of the composite of cardiovascular death, MI, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| 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 | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 350 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 42 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 42 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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