A Randomised, Double-Blind, 52-Week, Parallel-Group, Multicentre, Phase IIb Study to Evaluate the Effects of Rosuvastatin 10 mg, Rosuvastatin 40 mg and Atorvastatin 80 mg on Urinary Protein Excretion in Hypercholesterolaemic Diabetic Patients with Moderate Proteinuria PLANET I: Prospective evaLuation of proteinuriA and reNal function in diabETic patients with progressive renal disease - PLANET I

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-002510-38-DK
• Date of registration: 25/01/2006
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A Randomised, Double-Blind, 52-Week, Parallel-Group, Multicentre, Phase IIb Study to Evaluate the Effects of Rosuvastatin 10 mg, Rosuvastatin 40 mg and Atorvastatin 80 mg on Urinary Protein Excretion in Hypercholesterolaemic Diabetic Patients with Moderate Proteinuria PLANET I: Prospective evaLuation of proteinuriA and reNal function in diabETic patients with progressive renal disease - PLANET I
• Scientific title: A Randomised, Double-Blind, 52-Week, Parallel-Group, Multicentre, Phase IIb Study to Evaluate the Effects of Rosuvastatin 10 mg, Rosuvastatin 40 mg and Atorvastatin 80 mg on Urinary Protein Excretion in Hypercholesterolaemic Diabetic Patients with Moderate Proteinuria PLANET I: Prospective evaLuation of proteinuriA and reNal function in diabETic patients with progressive renal disease - PLANET I
• Date of first enrolment: 03/02/2006
• Target sample size: 345
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002510-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: study drug encapsulated for blinding If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: comparator encapsulated for blinding

Countries of recruitment

Denmark, Hungary, Italy

Key inclusion & exclusion criteria

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. Type 1 or 2 diabetes
4. 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
5. 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
6. 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.
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:
1. HbA1c > 11%
• For patients with HbA1c =11%, best achievable HbA1c should be maintained throughout the trial
2. History of statin intolerance, statin-induced myopathy, or serious hypersensitivity
reaction to other HMG-CoA reductase inhibitor (statin)
3. Previous rosuvastatin use <6 months prior to Visit 1
4. Use of oral or intravenous immunosuppressive medications for treatment of proteinuria and/or renal disease =3 months prior to Visit 1
5. 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
6. 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
7. Moderate to severe congestive cardiac failure (New York Heart Association
[NYHA] Class III or IV) (
8. Patients awaiting a planned myocardial revascularization prior to starting the study
9. 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
10. Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH)
>1.5 times ULN at Visit 1
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. Severe renal impairment, as judged by estimated GFR (MDRD equation) <40 ml/min/1.73m2 at Visit 3
19. 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
20. Statin therapy after Visit 1. Patients may be either statin naïve or have undergone statin withdrawal at Visit 1
21. Bile acid sequestrant therapy after Visit 2
• Bile acid sequestrant therapy will be allowed after Visit 7 (Week 14) at investigator discretion
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


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

Health Condition(s) or Problem(s) studied

Male and female patients aged >= 18 years with Type 1 or 2 diabetes, 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 <180 mg/dL (4.66 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.

Intervention(s)

Trade Name: Crestor 5mg
Product Name: Crestor 5mg encapsulated tablet
Product Code: AZD4522
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rosuvastatin
Current Sponsor code: AZD4522
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 5-

Trade Name: Lipitor 40mg
Product Name: Lipitor 40mg encapsulated tablet
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: atorvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Crestor 10mg
Product Name: Crestor 10mg encapsulated tablet
Product Code: AZD4522
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rosuvastatin
Current Sponsor code: AZD4522
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Crestor 20mg
Product Name: Crestor 20mg encapsulated tablet (2x 10mg)
Product Code: AZD4522
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rosuvastatin
Current Sponsor code: AZD4522
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): The primary outcome variable (end point) is the change in urinary protein/creatinine ratio from baseline to Week 52.

Main Objective: 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 patients with Type 1 or 2 diabetes, moderate proteinuria and hypercholesterolaemia.

Secondary Objective: 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

Secondary ID(s)

2005-002510-38-HU

D3569C00007