A Randomized, Double-Blind, Placebo Controlled, Multicenter, Phase III Study of Rosuvastatin (CRESTOR) 20 mg in the Primary Prevention of Cardiovascular Events Among Subjects with Low Levels of LDL Cholesterol and Elevated Levels of C-Reactive Protein - JUPITER

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2004-004094-28-GB
• Date of registration: 01/03/2005
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A Randomized, Double-Blind, Placebo Controlled, Multicenter, Phase III Study of Rosuvastatin (CRESTOR) 20 mg in the Primary Prevention of Cardiovascular Events Among Subjects with Low Levels of LDL Cholesterol and Elevated Levels of C-Reactive Protein - JUPITER
• Scientific title: A Randomized, Double-Blind, Placebo Controlled, Multicenter, Phase III Study of Rosuvastatin (CRESTOR) 20 mg in the Primary Prevention of Cardiovascular Events Among Subjects with Low Levels of LDL Cholesterol and Elevated Levels of C-Reactive Protein - JUPITER
• Date of first enrolment: 30/06/2005
• Target sample size: 15000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-004094-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Denmark, Estonia, Germany, Norway, United Kingdom

Key inclusion & exclusion criteria

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

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:
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



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

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Product Name: CRESTOR
Product Code: AZD4522
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rosuvastatin calcium
Current Sponsor code: AZD4522
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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. At the time of the subject's first cardiovascular event, blinded study therapy will be discontinued. The subject will continue to follow scheduled study assessments until study completion (defined as at least 520 primary endpoints having occured) and will be treated as deemed appropriate by the investigator.

Secondary Objective: 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.

Main Objective: 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).

Secondary ID(s)

2004-004094-28-NO

4522US/0011