E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
Primary objective: To confirm the efficacy of add-on therapy with LAF237 in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by testing the hypothesis that the HbA1c reduction with LAF237 is not inferior to that with gliclazide after 52 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Critical 1- To demonstrate safety of LAF237 in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by showing that add-on therapy with LAF237 has a similar adverse event profile compared to gliclazide after 52 weeks of treatment. 2- To demonstrate efficacy of add-on therapy with LAF237 in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by testing the hypothesis that the FPG reduction with LAF237 is not inferior to that with gliclazide after 52 weeks of treatment. 3- To demonstrate efficacy of add-on therapy with LAF237 in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by showing that the responder rates with LAF237 are similar to those with gliclazide after 52 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion criteria: Male or female (non-fertile or using a medically approved birth control method); age range 18-78 years inclusive; patients with type 2 diabetes who have received metformin for at least three months and have been on a stable dose of at least 1500 mg daily for a minimum of 4 weeks prior to visit 1; agreement to maintain the same dose of metformin throughout the study; body mass index (BMI) in the range of 22-45 kg/m2 inclusive; HbA1c 7.5% to 11% inclusive; FPG 15 mmol/L (270 mg/dL); and agreement to maintain prior diet and exercise. |
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E.4 | Principal exclusion criteria |
Exclusion criteria: Pregnant or lactating female; a history of type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes; acute metabolic diabetic complications within the past 6 months; evidence of significant diabetic complications; acute infections which may affect blood glucose control within 4 weeks prior to visit 1; a history of Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation; percutaneous coronary intervention within the past 3 months; myocardial infarction, coronary artery bypass surgery, unstable angina, or stroke within the past 6 months; congestive heart failure requiring pharmacologic treatment; second degree AV block (Mobitz 1 and 2), third degree AV block, prolonged QTc; malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years; liver disease; renal disease or renal dysfunction; acromegaly or treatment with growth hormone or similar drugs; concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study; donation of one unit (500 mL) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks; contraindications and warnings according to the country specific label for metformin or gliclazide not listed in the other exclusion criteria; known sensitivity to gliclazide or other sulfur containing drugs; treatment with any oral anti-diabetic other than metformin within 3 months prior to visit 1; chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months; chronic oral or parenteral corticosteroid treatment within 8 weeks prior to visit 1; treatment with class Ia, Ib and Ic or III anti-arrhythmics; investigational drug treatment within 4 weeks prior to visit 1 unless local health authority guidelines mandate a longer period; treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months; any of the following significant laboratory abnormalities: ALT, AST greater than 3 times the upper limit of the normal range, direct bilirubin greater than 1.3 times the upper limit of the normal range, serum creatinine levels ≥ 132 mol/L (1.5 mg/dL) males, ≥ 123mol/L (1.4 mg/dL) females, or a history of abnormal creatinine clearance, TSH outside of normal range at visit 1, clinically significant laboratory abnormalities confirmed by repeat measurement (other than hyperglycemia, hyperinsulinemia, and glycosuria), fasting triglycerides 7.9 mmol/L (> 700 mg/dL); history of active substance abuse (including alcohol) within the past 2 years; and potentially unreliable patients, and those judged by the investigator to be unsuitable for the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy parameters HbA1c measured by ion exchange High Performance Liquid Chromatography (HPLC).
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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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.5 | 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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |