E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
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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 demonstrate the efficacy of add-on therapy with vildagliptin 50 mg bid to metformin and glimepiride in patients with T2DM by testing the hypothesis that the HbA1c reduction with vildagliptin 50 mg bid is superior to that with placebo added to metformin and glimepiride after 24 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate the efficacy of add-on therapy with vildagliptin 50 mg bid to metformin and glimepiride in patients with T2DM by testing the hypothesis that the FPG reduction with vildagliptin 50 mg bid is superior to that with placebo after 24 weeks of treatment. 2. To evaluate the safety and tolerability of vildagliptin as add-on therapy to metformin and glimepiride in patients with type 2 diabetes inadequately controlled with combination of metformin and glimepiride as compared to placebo after 24-week treatment. 3. To evaluate the responder rate of vildagliptin 50 mg bid as add-on therapy to metformin and glimepiride in patients with type 2 diabetes, as compared to placebo after 24-week treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria Patients eligible for inclusion in this study must fulfill all of the following criteria: 1. Confirmed diagnosis of T2DM by standard criteria. 2. Treatment with oral anti-diabetic therapy, on stable dose for at least 12 weeks prior to the screening visit. Acceptable background anti-diabetic therapy includes: metformin (≥ 1500 mg) as monotherapy or in combination with SU, TZDs, or glinides at visit 1 with: • Monotherapy HbA1c ≥ 8.5 and ≤ 11.0% • Dual therapy HbA1c ≥ 7.5% and ≤ 11.0% 3. Age: ≥18 to ≤ 80 years at Visit 1. 4. HbA1c of ≥ 7.5 and ≤ 11.0% at Visit 105. 5. Body Mass Index (BMI) ≥22 to ≤45 kg/m2 at Visit 1. 6. Patients not already treated with glimepiride must be willing to switch to that drug. 7. Agreement to maintain the same dose of metformin (≥ 1500 mg) throughout the study. 8. Males or females 9. Females must be non-fertile female or female of childbearing potential using a medically approved birth control method based on local regulations: • A non-fertile female is defined as: post menopausal (12 months of natural spontaneous amenorrhea with serum FSH levels > 40 mIU/mL) or >6 and <12 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL); 6 weeks post bilateral o�phorectomy with or without hysterectomy; post hysterectomy; or sterilized by tubal ligation or otherwise assessed to be infertile • A female of childbearing potential is defined as any woman physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means. • Medically approved birth control method may include: hormonal contraceptives, intra-uterine device (IUD), and double-barrier contraception (if accepted by local regulatory authority and ethics committee). Acceptable methods of contraception may include total abstinence, including cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception • Reliable contraception should be maintained throughout the study for any female with childbearing potential.PLS SEE PROTOCOL |
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E.4 | Principal exclusion criteria |
Exclusion criteria 1. FPG ≥ 270 mg/dL (≥ 15.0 mmol/L) at Visit 1 and at Visit 105 (Week -1). 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) 3. Use of any of the following medications as assessed at Visit 1: • Use of weight control products including weight-loss medications • DPP-4 inhibitors, GLP-1 analogues/mimetics or insulin within the previous 6 months • Chronic oral (>7 consecutive days), parenteral or intra-articular corticosteroid treatment within 8 weeks prior to Visit 1 • Treatment with growth hormone within the previous 6 months • Treatment with any drug of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study. • Treatment with any oral anti-diabetic therapy other than metformin, SU, TZD and glinide within 12 weeks of Visit 1. 4. Any of the following significant laboratory abnormalities: • Clinically significant TSH outside of normal range at visit 1 • Clinically significant renal dysfunction as indicated by serum creatinine levels at Visit 1 and Visit 105: o Serum creatinine ≥ 1.5 mg/dL (132 μmol/L) for males and ≥ 1.4 mg/dL (123 μmol/L) for females • Elevated fasting triglycerides > 500 mg/dL (> 5.62 mmol/L) at visit 1, confirmed by a repeat measure within 3 working days • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Visit 1 or Visit 105 (Week -1), confirmed by repeat measure within 3 working days • Total bilirubin > 2 x ULN and/or direct bilirubin > ULN at Visit 1 or Visit 105 (Week-1), confirmed by repeat measure within 3 working days • Positive Hepatitis B surface antigen (HbsAg) at Visit 1 • Positive Hepatitis C antibody test (anti-HCV) at Visit 1 • Clinically significant laboratory abnormalities which in the opinion of the investigator, cause the patient to be considered inappropriate for inclusion in the study 5. A history or evidence of any of the following:• Acute metabolic conditions such as ketoacidosis, lactic acidosis or hyperosmolar state (including coma) within the past 6 months. • Current diagnosis of congestive heart failure (NYHA III or IV). • Myocardial infarction (MI) within the past 6 months • Coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months • Stroke or transient ischemic attack (TIA) within the past 6 months • Unstable angina within the past 3 months • Sustained and clinically relevant ventricular arrhythmia • Active substance abuse including alcohol (> 3 drinks per day on average and/or binge drinking of more than 5 drinks in 1 day during the last 6 months) and alcohol related history of disease within the past 2 years. • Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing’s syndrome or acromegaly-associated diabetes). • Malignancy of an organ system (other than localized basal cell carcinoma of the skin) treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases • Hepatic disorder defined as: • acute or chronic liver disease, evidence of hepatitis, cirrhosis or portal hypertension • history of imaging abnormalities that suggest liver disease (except hepatic steatosis), such as portal hypertension, capsule scalloping, cirrhosis • history of hypersensitivity, intolerance or a contraindication to the use of, sulfonylurea agents and metformin 6. Previous or current participation in a vildagliptin clinical trial 7. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. PLS SEE PROTOCOL |
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E.5 End points |
E.5.1 | Primary end point(s) |
primary efficacy variable : reduction in HbA1c |
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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 | No |
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) | 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) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |