| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | healthy subjects without prior history of MI, unstable angina, stroke or arterial revascularization who, on initial screening, are found to have LDL.C levels below 130 mg/dL (3.36 mmol/L) and CRP levels equal to or exceeding 2.0 mg/L | |
| 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 | | to investigate whether long-term treatment with rosuvastatin 20 mg compared with placebo will decrease the rate (based on time to first event after randomization) of major cardiovascular events (combined endpoint of cardiovascular death, stroke, myocardial infarction, unstable angina, or arterial revascularization) among individuals with low LDL C (<130 mg/dL [3.36 mmol/L]) who are at high vascular risk on the basis of an enhanced inflammatory response, as determined by elevated levels of CRP (equal to or exceeding 2.0 mg/L). | |
| E.2.2 | Secondary objectives of the trial | | to investigate the safety of long-term treatment with rosuvastatin compared with placebo through comparisons of total mortality, noncardiovascular mortality, and adverse events, and to investigate whether therapy with rosuvastatin reduces the incidence of diabetes mellitus, venous thromboembolic events, and the incidence of bone fractures. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1.Written informed consent to participate in the study
2.Men aged 50 years and over; women aged 60 years and over
3.Fasting LDL-C value <130 mg/dL (3.36 mmol/L) at Screening Visit 1
4.CRP value equal to or exceeding 2.0 mg/L at Screening Visit 1
5.TG <500 mg/dL (5.65 mmol/L) at Screening Visit 1
| |
| E.4 | Principal exclusion criteria | Any of the following is regarded as a criterion for exclusion from the study:
1. Treatment with any HMG-CoA reductase inhibitors or other lipid lowering therapies including fibric acid derivatives (fibrates), niacin (>50 mg per day), and bile acid sequestrants within 6 weeks of Screening Visit 1
2. History of serious hypersensitivity (including myopathy) reactions to other HMG CoA reductase inhibitors
3. Prior history of cardiovascular or cerebrovascular events such as MI, unstable angina, prior arterial revascularization, or stroke, or CHD risk equivalent as defined by NCEP ATP III
4. Current use of postmenopausal oral hormone replacement therapy (HRT)
5. Current treatment with cyclosporin, tacrolimus, azathioprine, or other immunosuppressants including chronic use of oral glucocorticoids
6. Active liver disease or hepatic dysfunction or elevations of ALT >2 x ULN at Screening Visit 2
7. Baseline elevations of CK >3 x ULN at Screening Visit 2
8. Serum creatinine >2.0 mg/dL (177 umol/L) at Screening Visit 2
9. Diabetes mellitus, as defined by FSG >126 mg/dL (7.0 mmol/L) at Screening Visit 2 or by the use of insulin and/or an oral hypoglycemic agent
10. Uncontrolled hypertension, defined as systolic blood pressure >190 mmHg or a diastolic blood pressure >100 mmHg at Screening Visit 2.
11. History of malignancy within the past 5 years, with the exception of basal cell or squamous cell carcinoma of the skin (women with a history of cervical dysplasia should be excluded unless 3 consecutive normal cervical smears, Papanicolaou (Pap) smears, have been recorded subsequently before entry)
12. Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH) >1.5 x ULN at Screening Visit 2 or subjects whose thyroid replacement therapy was initiated or modified within the last 3 months.
13. Chronic inflammatory condition such as severe arthritis, lupus, or inflammatory bowel disease
14. History of alcohol or drug abuse within the past 1 year
15. Participation in another investigational drug study <30 days before enrollment or according to the participants local ethics committee requirements where a longer period is stipulated
16. Prior participation in this study
17. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful participation in the study
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary study endpoint will consist of the first occurrence of a major cardiovascular event after randomization; it will be either cardiovascular death, stroke, myocardial infarction, unstable angina, or arterial 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| 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 | No |
| 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.8.5 | 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 | |
| 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 | | Database lock defines the end of the study. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
