E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetic Microalbuminuria |
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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 | 10027525 |
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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 |
The objective of this study is to determine the safety and efficacy of sulodexide in the treatment of patients with type 2 diabetes and persistent microalbuminuria, despite being treated with a maximum approved dose of an angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI).
The primary efficacy measure will be the percentage of patients achieving “therapeutic success,” which is defined as a composite binary endpoint of conversion from microalbuminuria to normoalbuminuria (ACR <25 mg/G [2.8 mg/mmol] for men and ACR <35 mg/G [4.0 mg/mmol] for women) and at least a 25% reduction in ACR level relative to baseline at Week 26 or a >50% reduction in ACR level relative to baseline at Week 26. |
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E.2.2 | Secondary objectives of the trial |
The secondary efficacy measures will include: 1) percentage of patients achieving normoalbuminuria at Weeks 8, 16, and 26 on therapy, and at Weeks 30 and 34 (4 and 8 weeks off therapy, respectively); 2) percentage of patients achieving >50% reduction in ACR from baseline at Weeks 8, 16, and 26 on therapy, and at Weeks 30 and 34 (4 and 8 weeks off therapy, respectively); 3) observed ACR, and change from baseline in ACR at Weeks 8, 16, and 26 on therapy, and at Weeks 30 and 34 (4 and 8 weeks off therapy, respectively); 4) percentage of patients reaching an ACR more than or equal to 200 mg/G (22.6 mg/mmol) at Weeks 8, 16, and 26 on therapy, and at Weeks 30 and 34 (4 and 8 weeks off therapy, respectively); and 5) percentage change from baseline on various additional endpoints, including serum creatinine, Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate (GFR), and serum albumin.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The principle inclusion criteria for the study includes men and women with type 2 diabetes and persistent microalbuminuria (in men urine albumin creatinine ratio [ACR] 35 – 200 mg albumin/G creatinine [4.0 - 22.6 mg/mmol], in women urine ACR 45 – 200 mg albumin/G creatinine [5.1 – 22.6 mg/mmol] based on the geometric mean of 3 first voided AM urine samples at the qualifying visit [Visit 6]). Patient’s serum creatinine must be less than or equal to 1.5 mg/dL at screening. |
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E.4 | Principal exclusion criteria |
1. Age of onset of type 2 diabetes <18 years;
2. HbA1C >10.0%;
3. Morbid obesity defined as a body mass index (BMI) more than or equal to 45 kg/m2;
4. Type 1 (insulin-dependent; juvenile onset) diabetes;
5. Renal disease as follows: Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable); Renal allograft;
6. Absolute requirement for combination therapy of ACEI and ARB;
7. Known allergies or intolerance to any heparin-like compound;
8. Untreated urinary tract infection that would impact urinary protein values; or
9. Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Patients assigned to sulodexide 200 mg will achieve a significantly higher fraction of patients with “therapeutic success” at Week 26, as defined by the composite binary endpoint of conversion from microalbuminuria to normoalbuminuria (ACR <25 mg/G [2.8 mg/mmol] for men and ACR <35 mg/G [4.0 mg/mmol] for women) and at least a 25% reduction in ACR level relative to baseline at Week 26 or a >50% reduction in ACR level relative to baseline at Week 26. The primary efficacy analysis will be implemented by Fisher’s exact test.
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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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 study will terminate after all patients are randomized and have been in the study through the end of the Washout Period. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |