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 demonstrate the efficacy of initial fixed combination treatment with vildagliptin and metformin in drug naïve patients with T2DM by testing the hypotheses that the HbA1c reduction with fixed combination (high or low dose) of vildagliptin and metformin is superior to that of both individual monotherapy components after 24 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
1.To demonstrate dose-sparing properties of initial fixed combination treatment with vildagliptin and metformin in drug naïve patients with T2DM by demonstrating that the HbA1c reduction with lower final doses in the fixed combination of vildagliptin and metformin is comparable to (or better but not statistically significant) that of both individual monotherapy components with an improved safety and tolerability profile after 24 weeks of treatment. 2.To demonstrate efficacy of initial fixed combination treatment with vildagliptin and metformin in drug naïve patients with T2DM by testing the hypotheses that the fasting plasma glucose (FPG) reduction with the fixed combination (high or low dose) of vildagliptin and metformin is superior to that of both individual monotherapy components 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 | No |
E.3 | Principal inclusion criteria |
1. Drug naïve patients with T2DM (for the purposes of this protocol “drug naïve” patients are defined as subjects who have never been treated with an antidiabetic agent or subjects who have not taken any antidiabetic agent for at least 12 weeks prior to study entry (Visit 1) and if they have received oral antidiabetic agents then never for > 3 months at any time in the past). 2. Age in the range of 18-78 years inclusive. 3. Male, non-fertile female or female of childbearing potential using a medically approved birth control method, based on local regulations and may include: • 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. 4. Diagnosis of T2DM for at least 4 weeks prior to study entry (Visit 1). 5. Body mass index (BMI) in the range of 22-40 kg/m2 inclusive at visit 1. 6. HbA1c in the range of 7.5 to 11% inclusive at visit 1. 7. FPG < 270 mg/dL (15 mmol/L) at visit 1 (measurement may be repeated once to confirm FPG value). 8. Agreement to maintain prior diet and exercise habits during the full course of the study. 9. Written informed consent to participate in the study. 10. Ability to comply with all study requirements.
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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 condition that may interfere with the interpretation of efficacy and safety data during the study. 5. 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 or percutaneous coronary intervention; • unstable angina or stroke. 6. Congestive heart failure (CHF) requiring pharmacological treatment. 7. Any of the following ECG abnormalities: • Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation • second degree AV block (Mobitz 1 and 2) • third degree AV block • prolonged QTc (> 500 msec) 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. 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. 11. Contraindications and warnings according to the country specific label for metformin not listed in the other exclusion criteria. 12. Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 month. 13. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1. 14. Treatment with growth hormone or similar drugs. 15. Treatment with class Ia, Ib and Ic or III anti-arrhythmics. 16. Patients who have already been in a study of vildagliptin or another DDP 4 inhibitor. 17. 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. 18. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e., cytostatic drugs). 19. Any of the following significant laboratory abnormalities: • ALT, AST greater than 2 times the upper limit of the normal range at visit 1,confirmed by a repeat measure within 3 working days • Total bilirubin greater than 2 times upper limit of the normal range and direct bilirubin greater than the upper limit of the normal range at visit 1,confirmed by a repeat measure within 3 working days • A Positive Hepatitis B test (surface antigen-HBsAg) • A Positive Hepatitis C test (HCV antibodies) • Clinically significant renal dysfunction as indicated by serum creatinine levels ≥ 1.5 mg/dL (132 µmol/L) males, ≥ 1.4 mg/dL (123 µmol/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. 20. History of active substance abuse (including alcohol) within the past 2 years.
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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 an 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 -2, visit 1) if the 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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 112 |
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 | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |