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 |
To confirm the efficacy of vildagliptin 100 mg add-on therapy in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by testing the hypothesis that the HbA1c reduction with vildagliptin 100 mg qd (given as an a.m. dose) is superior to that with placebo after 24 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
1. To confirm the safety of vildagliptin in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by showing that add-on therapy with vildagliptin 100 mg qd (pooled data of a.m and p.m. dosing) has comparable AE profiles including gastrointestinal (GI) tolerability to placebo during 24 weeks of treatment. 2. To confirm the efficacy of add-on therapy with vildagliptin in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by testing the hypothesis that the FPG reduction with vildagliptin 100 mg qd (given as an a.m. dose) is superior to that with placebo after 24 weeks of treatment. For detailed list of secondary objectives see full protocol |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male, non-fertile female or female of childbearing potential using a medically approved birth control method. • A non-fertile female is defined as: post menopausal (12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/m); 6 weeks post bilateral oophorectomy with or without hysterectomy; post hysterectomy; or sterilized by tubal ligation. • 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 include: hormonal contraceptives, IUD, and double-barrier contraception. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in 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. 2. Patients 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. 3. Agreement to maintain the same dose of metformin throughout the study. 4. Age in the range of 18-78 years inclusive. 5. Body mass index (BMI) in the range of 22 - 40 kg/m2 inclusive at visit 1.
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating female. 2. A history of: • type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly. • acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months. 3. Evidence of significant diabetic complications, e.g. symptomatic autonomic neuropathy or gastroparesis. 4. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical conditions that may interfere with the interpretation of efficacy and safety data during the study. 5. A history of: • Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation. • percutaneous coronary intervention within the past 3 months. • any of the following within the past 6 months: myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor); coronary artery bypass surgery; unstable angina; or stroke. 6. Congestive heart failure requiring pharmacologic treatment. 7. Any of the following ECG abnormalities: • second degree AV block (Mobitz 1 and 2) • third degree AV block • prolonged QTc (> 500 ms) 8. Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years. 9. Liver disease such as cirrhosis or chronic active hepatitis. 10. Significant renal dysfunction (see also exclusion criteria 20 laboratory abnormalities). 11. 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. 12. Contraindications and warnings according to the country specific label for metformin not listed in the other exclusion criteria. 13. Treatment with any oral anti-diabetic other than metformin within 3 months prior to visit 1 14. Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months. 15. Treatment with growth hormone or similar drugs. 16. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1. 17. Treatment with class Ia, Ib and Ic or III anti-arrhythmics. 18. Use of other investigational drugs at visit 1, or within 30 days or 5 half-lives of visit 1, whichever is longer, unless local health authority guidelines mandate a longer period. 19. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e. cytostatic drugs). 20. Any of the following significant laboratory abnormalities: • ALT, AST greater than 3 times the upper limit of the normal range at visit 1. • Direct bilirubin greater than 1.3 times the upper limit of the normal range at visit 1. • Serum creatinine levels ≥ 1.5 mg/dL (132 mol/L) males, ≥ 1.4 mg/dL (123 mol/L) females, or a history of abnormal creatinine clearance. • Clinically significant TSH values outside of normal range at visit 1. • Clinically significant laboratory abnormalities, confirmed by repeat measurement, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1. • Fasting triglycerides > 700 mg/dL (7.9 mmol/L) at visit 1. 21. History of active substance abuse (including alcohol) within the past 2 years and potentially unreliable patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is change from baseline in HbA1c at Week 24 or at the final visit with HbA1c measurement for those patients who do not have a Week 24 HbA1c measurement (the last observation carried forward (LOCF) approach). Baseline is the measurement obtained on the day of randomization (Day 1, visit 2), or the screening measurement (Week -4, visit 1) if Day 1 measurement is missing. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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) | 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
| Information not present in EudraCT |
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 | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |