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/mL); 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 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. • Females using hormonal contraceptives must use a non-hormonal medically approved birth control method in addition during the full course of the study. 2. Patients who have received metformin for at least three months and have been on 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 to 77 years inclusive. 5. Body mass index (BMI) in the range of 22-45 kg/m2 inclusive at visit 1. 6. HbA1c in the range of 7.5 to 11% 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 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. 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 (NYHA class I-IV). 7. Any of the following ECG abnormalities: • second degree AV block (Mobitz 1 and 2) • third degree AV block • prolonged QTc interval (> 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 23 laboratory abnormalities). 11. Acromegaly or treatment with growth hormone or similar drugs. 12. Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study. 13. 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. 14. Contraindications and warnings according to the country specific label for metformin or pioglitazone not listed in the other exclusion criteria. 15. Known sensitivity to pioglitazone, rosiglitazone or similar drugs. 16. Treatment with any oral anti-diabetic drug other than metformin within 3 months prior to visit 1. 17. Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months. 18. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1. 19. Treatment with class Ia, Ib and Ic or III anti-arrhythmics. 20. Thyroid hormone replacement is allowed if the dosage has been stable for at least 3 months. 21. 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. 22. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (e.g.. cytostatic drugs). 23. Any of the following significant laboratory abnormalities: • ALT, AST greater than 2.5 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 = 132 µmol/L (=1.5 mg/dL) males, = 123 µmol/L (=1.4 mg/dL) females. • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate 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 HbA1c reduction with vildagliptin is not inferior to that with pioglitazone at Week 52.;Secondary Objective: 1. To demonstrate the safety of vildagliptin in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by showing that add-on therapy with vildagliptin has a favorable adverse event profile (including peripheral edema) compared to pioglitazone at Week 52. 2. To demonstrate 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 is not inferior to that with pioglitazone at Week 52. 3. To demonstrate the ancillary clinical benefits of add-on therapy with vildagliptin in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy by testing the hypothesis that vildagliptin has a favorable effect on body weight relative to pioglitazone at Week 52. For complete list please refer to full protocol;Primary end point(s): The primary efficacy variable is change from baseline in HbA1c at Week 52 or at the final visit with HbA1c measurement for those patients who do not have a Week 52 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. | — |
Countries
Germany, Italy, Spain, United Kingdom
Outcome results
None listed