Type II Diabetes
Conditions
Interventions
Product Name: Vildagliptin
Product Code: LAF237A
Pharmaceutical Form: Tablet
INN or Proposed INN: Vildagliptin
Concentration unit: mg mi
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 =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 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 •
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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; Secondary Objective: 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 ;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. | — |
Countries
Germany, Hungary, Italy, Sweden, United Kingdom
Outcome results
None listed