E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients affected by type 2 diabetes mellitus (HbA1c≥ 7%)treated with Metformin alone |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10012602 |
|
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 assess a superior efficacy and durability of the DPP-IV inhibitor Vildagliptin as an add-on treatment to Metforminin in comparison to Glibenclamide in terms of achievement and maintenance of a good glycemic control (HbA1c < 7%) in type 2 diabetic patients in failure with Metformin as monotherapy over a period of 36 months |
|
E.2.2 | Secondary objectives of the trial |
-Primary objective measured at the end of follow-up(including Extension Phase),measured as % of patient developing primary or secondary failure with the association of Metformin plus one of the two experimental treatments(Glibenclamide or Vildagliptin-Absolute change of HbA1c on the short-term(month 4,V2)and long-term(month 36,V12)compared to randomization(V0)-Percent of patients achieving HbA1c goal(<7%)on the short-term(month 4,V2)-Percent of patients developing secondary failure(defined as HbA1c &#8805;7% from V4 to the end of the experimental period)among the ones who achieve HbA1c < 7% within 8 months(V3-Time on months from the first treatment dose to the occurrence of treatment failure based on the definition used for primary end-point determination-Absolute and percent change in body weight at 36 months(V12)compared to randomization(V0)-Long-term safety and tolerability as total number and type of adverse events-Long-term change in insulin secretion |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age equal or above 35 years; 2. Diagnosis of type 2 diabetes mellitus as defined by the American Diabetes Association , with at least one year of disease duration at the time of the screening visit; 3. Blood glucose lowering treatment with Metformin alone (monotherapy) at a stable dose of at least 1.5 g/day (or maximum tolerated dose) in the 3 months prior to the screening visit; 4. Insufficient metabolic control as defined by recent (last six months) HbA1c &#8805; 7% in any peripheral laboratory and confirmed at the time of the screening; 5. Absence of a recent clinically-relevant progression of micro- and macro-vascular complications (see exclusion criteria); 6. Written informed consent to participate into the study. |
|
E.4 | Principal exclusion criteria |
1. Age below 35 years 2. Type 1 diabetes or other causes of diabetes (pancreatectomy, gestational diabetes, etc.) 3. HbA1c < 7% or &#8805; 10% at the screening visit 4. Treatment with any blood glucose lowering treatment other than Metformin in the three months before screening visit 5. BMI < 20 or &#8805; 40 kg/m2, or current/ past history of clinically-relevant eating disorders (including -but no limited to- nervous anorexia, bulimia, binge-eating disorder, etc.) 6. Significant progression of diabetic macro-angiopathy or cardiovascular disease in the six months prior to study visit, including: a. Acute myocardial infarction or acute coronary syndrome requiring hospitalization; b. Acute cerebro-vascular event requiring hospitalization; c. Acute limb ischemia or new onset of clinically-relevant peripheral artery disease (as defined by claudication + positive ABI test); d. New limb ulceration of suspected vascular origin or new onset of a diabetic foot or significant progression of pre-existing lesions; e. Any revascularization procedure (by-pass, stenting, angioplasthy, trombo-endarterectomy, etc.) in any arterial district; 7. Significant progression of diabetic micro-angiopathy in the six months prior to study visit, including: a. Proliferative retinopathy, or progression of severity of more than one step, or new macular edema likely to be laser-treated. Steps of diabetic retinopathy: absent, background, mild non-proliferative, moderate-to-severe non-proliferative, proliferative; b. Increase of at least 0.5 mg/dL of plasma creatinine or progression to macro-proteinuria; c. Onset of clinically-relevant neuropathy d. Onset of erectile dysfunction 8. Organ failure or other severe diseases limiting life expectancy; 9. Ongoing pregnancy or absence of effective contraception in women with childbearing potential 10. Contraindications to the maintenance of the background therapy (Metformin), including but not limited to- chronic kidney failure or plasma creatinine concentrations > 1.5 mg/dL, severe respiratory failure, etc.; 11. Contraindications to the use of a Sulfonylurea; 12. Contraindications to the use of a DPP-IV Inhibitor; 13. Laboratory findings, or other disease conditions, at the screening visit that might interfere with study measurements: a. Hemoglobinopathy known to affect HbA1c assays; b. Known chronic liver diseases, including HBV and HCV infection; c. Liver makers (AST, ALT, ALP, GGT, bilirubin) above 2 times the upper normal limit; d. Amylase above 2 times the upper normal limit; 14. Chronic use of systemic corticosteroids; 15. History of low compliance, clinically-relevant psychiatric disorders or any current/ historical finding suggesting the patient as inappropriate to follow the study procedures. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent of patient developing primary or secondary failure with the association of Metformin plus one of the two experimental treatments (Glibenclimide or Vildagliptin). Primary failure is defined as HbA1c &#8805; 8% at V2 (four months of follow-up) or HbA1c &#8805; 7% at V3 (eight months of follow-up). Secondary failure is defined as HbA1c &#8805; 7% after V3 (from V4 to V12 included). |
|
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
| |
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 | 0 |
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 | 0 |