E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Overt Type 2 Diabetic Nephropathy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061835 |
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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 determine whether sulodexide, compared to placebo, increases the time to the first occurrence of the composite end point of doubling of the serum creatinine from baseline, or end-stage renal disease (ESRD) in patients with diabetic nephropathy due to type 2 diabetes; and to compare the safety and tolerance of sulodexide with placebo when administered long-term to patients with diabetic nephropathy due to type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
To determine whether sulodexide, compared to placebo: decreases the incidence rate of the composite endpoint of a doubling of the serum creatinine from baseline or ESRD in patients with diabetic nephropathy due to type 2 diabetes, increases the time to the individual outcomes of a doubling of the serum creatinine from baseline and ESRD in patients with diabetic nephropathy due to type 2 diabetes, decreases the incidence rates of the individual outcomes of a doubling of the serum creatinine from baseline and ESRD in patients with diabetic nephropathy due to type 2 diabetes, decreases urinary protein excretion as measured by protein creatinine ratio (PCR) and albumin creatinine ratio (ACR) in patients with diabetic nephropathy due to type 2 diabetes, and changes all-cause mortality. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Males and non-lactating and non-pregnant females. Females must be post-menopausal, surgically sterile, or using adequate contraception. All women of child-bearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L of β-HCG) at Visit 1 and within 72 hours prior to the start of study medication;
2. Diagnosis of type 2 diabetes as defined by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus;
3. Age 18 years old. Upper age limit is at the discretion of the investigator and should be based on the judgment of the investigator that the patient is likely to survive at least 2 years;
4. Total protein from a 24-hour urine collection at Visit 2 is equal or more than 900 mg/24 hr (equal or more than 0.9 G/24 hr);
5. Serum creatinine in women between 1.3 and 3.0 mg/dL (115-265 μmol/L), inclusive, and in men between 1.5 and 3.0 mg/dL (133-265 μmol/L), inclusive, at Visit 1. If the screening serum creatinine falls outside the specified creatinine criteria, a patient may enter the Run-in Period if the GFR by the MDRD formula at Visit 1 is between 25 to 45mL/min;
6. Willing to discontinue antihypertensive medication regimen, if applicable.
7. Willing and able to give informed consent.
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E.4 | Principal exclusion criteria |
1. Type 1 (insulin-dependent; juvenile onset) diabetes;
2. Renal disease as follows:· Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable), or· Renal allograft;
3. Absolute requirement for combination therapy of ACEI and ARB;
4. Patients who require ACEI, but not ACEI/ARB combination, may enter the trial if approved by the Clinical Coordinating Center;
5. Cardiovascular disease as follows: · Unstable angina pectoris within 3 months of study entry; · Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 months of study entry; · Transient ischemic attack within 3 months of study entry; · Cerebrovascular accident within 3 months of study entry; · New York Heart Association Functional Class III or IV (Note: if a patient is New York Heart Association Functional Class I or II and requires an ACEI, consult with the Clinical Coordinating Center to obtain permission for the patient to be on an ACEI rather than an ARB); · Obstructive valvular heart disease or hypertrophic cardiomyopathy; or · Second or third degree atrioventricular block not successfully treated with a pacemaker;
6. Need for chronic (>2 weeks) immunosuppressive therapy, including corticosteroids (excluding inhaled or nasal steroids);
7. New diagnosis of cancer or recurrent cancer within 5 years of screening (except non-melanoma skin cancer);
8. Psychiatric disorder that interferes with the patient’s ability to comply with the protocol;
9. Inability to tolerate oral medication or a history of significant malabsorption;
10. History of alcohol or other drug abuse within 12 months of study entry;
11. Known human immunodeficiency virus disease;
12. Any other medical condition which renders the patient unable to or unlikely to complete the study, or which would interfere with optimal participation in the study or produce significant risk to the patient;
13. Receipt of any investigational drugs (including placebo) within 30 days of enrollment;
14. Evidence of hepatic dysfunction including total bilirubin >2.0 mg/dL (>35 mmol/L) or liver transaminase (aspartate aminotransferase [AST] or alanine transferase [ALT]) >3 times upper limit of normal at Screening;
15. Anticipate need for surgery;
16. Inability to cooperate with study personnel or history of noncompliance to medical regimen, (i.e., patients who would be expected to comply poorly with treatment);
17. Known allergies or intolerance to any heparin-like compound including heparin-induced thrombocytopenia Type II;
18. Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study.
19. Untreated urinary tract infection that may impact urinary protein values. |
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E.5 End points |
E.5.1 | Primary end point(s) |
This is a maximal event trial that has been designed to enroll approximately 2240 patients and to follow these patients until approximately 500 composite endpoints have occurred or the DSMC recommends the trial be closed due to either efficacy or futility. The primary hypothesis is to test whether sulodexide (200 mg) as compared to placebo will significantly increase the time to the first occurrence of the composite endpoint of a doubling of the serum creatinine from baseline or ESRD in patients with diabetic nephropathy due to type 2 diabetes. |
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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 | 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 | 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) | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 125 |
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 |
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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
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The end-of-trial (completion) date is when all patients have completed all study visits or have otherwise discontinued from the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |