| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Male and female, non-diabetic patients aged ≥18 with moderate proteinuria (baseline urinary protein/creatinine ratio ≥500 mg/g and ≤5000 mg/g), hypercholesterolaemia (fasting LDL-C ≥90 mg/dL (2.33 mmol/L) and receiving current treatment with ACE (Angiotensin converting enzyme) inhibitors and/or ARBs (Angiotensin receptor blockers) for ≥3 months prior to Visit 1. |
|
| 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 of this study is to evaluate the effects of rosuvastatin and atorvastatin on urinary protein excretion by evaluation of the change in urinary protein/creatinine ratio from baseline to Week 52 in non-diabetic patients with moderate proteinuria and hypercholesterolaemia. |
|
| E.2.2 | Secondary objectives of the trial |
1. to evaluate the effects of rosuvastatin and atorvastatin on urinary protein excretion by evaluation of the change in urinary protein/creatinine ratio
2. to evaluate the effects of rosuvastatin and atorvastatin on urinary albumin excretion by evaluation of the change in urinary albumin/creatinine ratio
3. to evaluate the effects of rosuvastatin and atorvastatin on: low-density lipoprotein
cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), nonHDL-C, apolipoprotein A1 (ApoA-1), apolipoprotein B (ApoB),
TC/HDL-C, LDL-C/HDL-C, nonHDL-C/HDL-C and ApoB/ApoA-1) to explore the
relationship between renal effects and lipid changes
4. to evaluate the effects of rosuvastatin and atorvastatin on renal function by evaluation of the change in estimated glomerular filtration rate (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) [Levey et al 1999] equation |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
For inclusion in the study lead-in period at Visit 1, patients must fulfill all of the following criteria:
1. Provision of written informed consent
2. Male or female aged ≥18
3. Fasting LDL-C levels collected at Visit 1:
≥90 mg/dL (2.33 mmol/L) if patient has not taken statin therapy within 2 weeks of Visit 1
≥60 mg/dL (1.55 mmol/L) if patient has taken statin therapy within 2 weeks of Visit 1
4. Proteinuria as evidenced by one or more of the following criteria at Visit 1:
a. Urinary dipstick for protein ≥ 1+ (clinic and/or central laboratory), or
b. One or more of the following documented ≤3 months prior to Visit 1:
•Urinary protein to creatinine ratio ≥500 mg/gm to ≤5000 mg/gm
•24-hour urinary protein excretion ≥500 mg to ≤5000 mg
•Urinary albumin to creatinine ratio ≥350 mg/gm to ≤3500 mg/gm
•24-hour urinary albumin excretion ≥350 mg to ≤3500 mg
5. Stable and individually optimized treatment with ACE inhibitor and/or an ARB for ≥3 months prior to Visit 1
-- See protocol for continuation in the lead-in period after Visit 1 and for inclusion into the randomised treatment period. |
|
| E.4 | Principal exclusion criteria |
1. History of statin intolerance, statin-induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitor (statin)
2. Previous rosuvastatin use < 6 months prior to Visit 1
3. Bile acid sequestrant therapy after Visit 2
• Bile acid sequestrant therapy will be allowed after Visit 7 (Week 14) at investigator discretion
4. Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have a positive serum pregnancy test (a serum b-Human chorionic gonadotropin [beta-HCG] analysis)
5. Patients having one or more of the following events within 12 weeks of V1: a myocardial infarction, unstable angina, myocardial revascularization (percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or another revascularization procedure) or a transient ischemic attack (TIA) or stroke
6. Moderate to severe congestive cardiac failure (New York Heart Association [NYHA] Class III or IV)
7. Patients awaiting a planned myocardial revascularization prior to starting the study, i.e. planned prior to Visit 1
8. History of malignancy (unless a documented disease-free period exceeding 5 years is present) with the exception of basal cell or squamous cell carcinoma of the skin. Women with a history of cervical dysplasia would be permitted to enter the study provided they have 3 consecutive clear Papanicolaou (Pap) smears
9. Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH)
>1.5 times ULN at Visit 1
10. Type I or II diabetes
11. History of homozygous familial hypercholesterolaemia or known Type III hyperlipoproteinemia (familial dysbetalipoproteinemia)
12. History of alcohol or drug abuse, or both in the last 5 years
13. Current active liver disease as defined by elevations of >2 x ULN in ALT at
Visits 1 or 3 or severe hepatic impairment
14. Unexplained creatine kinase (CK) > 2 x ULN at Visits 1 and 3
15. Participation in another investigational drug study <4 weeks before Visit 1 or in accordance with local ethics if a longer period is stipulated. Patients who withdrew from the treatment phase of this or a previous rosuvastatin study cannot re-enter this study
16. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient’s safety or successful participation in the study
17. Patients whose hormone replacement therapy (HRT) or oral contraceptive therapy (OCT) was initiated or changed within the 3 months prior to Visit 1
18. Use of oral or intravenous immunosuppressive medications ≤3 months prior to Visit 1
19. Severe renal impairment, as judged by estimated GFR (MDRD equation) <40 ml/min/1.73m2 at Visit 3
20. Any known clinical condition that, in the opinion of the investigator, would require an adjustment of the ACE inhibitor and/or ARBs after Visit 1
21. Statin therapy after Visit 1. Patients may be either statin naïve or have undergone statin withdrawal at Visit 1
22. Underlying renal disease attributed to autosomal dominant polycystic kidney disease, primary idiopathic intersitial nephritis, HIV (human immunodeficiency virus) nephropathy or ischemic renal disease due to bilateral renal artery stenosis or unilateral renal artery stenosis in a single kidney
23. Asian ethnicity
24. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary outcome variable (end point) is the change in urinary protein/creatinine ratio from baseline to Week 52. |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| 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 |
| study drug encapsulated for blinding |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| comparator encapsulated for blinding |
|
| 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 | 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
|
| End of trial is defined as the date of the last visit of the last patient |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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