Type II Diabetes
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 and IUD. 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 patient 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 with type 2 diabetes who have received metformin for at least 3 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 30-78 years. 5. Body mass index (BMI) in the range of 22-35 kg/m2 inclusive at visit 1. 6. HbA1c in the range of 6.5 to 9.0 % inclusive at visit 1. 7. FPG =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating female. 2. A history of: • Type 1 diabetes, diabetes that is a result of pancreatic injury, or other secondary forms of diabetes, e.g., Cushing’s syndrome and acromegaly. • Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma). 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. 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 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. Significant renal dysfunction (see also exclusion criteria 21 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. In addition, patients with anemia, as defined by hemoglobin 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 2 times the upper limit of the normal range (ULN) at visit 1, confirmed by a repeat measure within 3 working days. • Total bilirubin greater than 2 times ULN 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). • Serum creatinine levels = 1.5 mg/dL (132 µmol/L) males, = 1.4 mg/dL (123µmol/L) females, or a history of abnormal creatinine clearance. • Clinically significant TSH outside of normal range at visit 1; thyroid hormone replacement is allowed if the dosa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To demonstrate the effect of vildagliptin on the incretin mediated enhancement of insulin secretion (75 g oral glucose vs. matched i.v. glucose) in patients with T2DM treated with metformin by testing the hypothesis that the improvement of the incretin effect assessed as C-peptide IAUC(0-4hr) with vildagliptin 100 mg qd is superior to that with placebo after 2 weeks of treatment.;Primary end point(s): Assessment of the effect of vildagliptin on the incretin mediated enhancement of insulin secretion in patients with T2DM . The primary efficacy variable is incretin effect assessed as [C-peptide IAUC(0-4hr) (oral) – C-peptide IAUC(0-4hr) (i.v.)] / [C-peptide IAUC(0-4hr) (oral)] x 100%. ;Secondary Objective: 1. To demonstrate the effect of vildagliptin on the incretin mediated enhancement of insulin secretion (75 g oral glucose vs. matched i.v. glucose) in patients with T2DM treated with metformin by testing the hypothesis that the improvement of the incretin effect assessed as ‘insulin secretion rate (ISR) relative to glucose (0-2hr)’ (see Section 10.5.1 for details) with vildagliptin 100 mg qd is superior to that with placebo after 2 weeks of treatment. 2. To evaluate the prandial responses to vildagliptin in patients with T2DM treated with metformin by testing the hypothesis that vildagliptin 100 mg qd has favorable effects relative to placebo on postprandial parameters (derived from C-peptide, insulin, glucagon, GLP-1, and GIP) following an oral glucose challenge or “isoglycemic” intravenous glucose infusion after 2 weeks of treatment. | — |
Countries
Germany
Outcome results
None listed