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 micromol/L (1.5 mg/dL) males, ≥ 123 micromol/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 | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |