Type II Diabetes
Conditions
Interventions
Product Name: Vildagliptin
Product Code: LAF237
Pharmaceutical Form: Tablet
INN or Proposed INN: Vildagliptin
CAS Number: 274901-16-5
Current Sponsor code: LAF273
Concentration unit: mg milligram(s)
C
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria (assessed during screening): 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. Age in the range of 18-78 years inclusive. 3. Patients with T2DM who have taken 850-1000 mg daily dose of metformin monotherapy for at least 2 months immediately prior to visit 1. 4. Diagnosis of T2DM for at least 2 months prior to study entry (visit 1). 5. Body mass index (BMI) in the range of 22-45 kg/m2 inclusive at visit 1. 6. HbA1c in the range of 6.5-9% inclusive at visit 1. 7. FPG =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria (assessed during screening): 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, gastroparesis, as well as symptoms of worsening hyperglycemia (i.e. polyuria, polydipsia, weight loss) in the absence of any intercurrent illness or other incidental circumstances potentially causing deterioration of glucose control. 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. Contraindications and warnings according to the country specific label for metformin not listed in the other exclusion criteria. 11. Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months. 12. Treatment with other oral antidiabetics within 3 months prior to visit 1. 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. 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. 17. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e., cytostatic drugs). 18. 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 repeat measurement within 3 working days. • Total bilirubin greater than 2 times the upper limit of the normal range and/or direct bilirubin greater than the upper limit of the normal range at visit 1,confirmed by repeat measurement 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 abnormal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of vildagliptin 100 mg qd used in combination with metformin 500 mg bid in patients with type 2 diabetes inadequately controlled on metformin 500 mg bid monotherapy by testing the hypothesis that the hemoglobin A1c (HbA1c) reduction with the combination is not inferior to that with upward titration of metformin up to 1000 mg bid monotherapy after 24 weeks of treatment. ;Secondary Objective: 1. To evaluate the safety of vildagliptin 100 mg qd used in combination with metformin 500 mg bid in patients with type 2 diabetes inadequately controlled on metformin 500 mg bid monotherapy by showing that patients treated with the combination of vildagliptin 100 mg qd and metformin 500 mg bid have a similar adverse event profile compared to those treated with metformin up to 1000 mg bid after 24 weeks of treatment. 2. To evaluate GI tolerability of vildagliptin 100 mg qd used in combination with metformin 500 mg bid in patients with type 2 diabetes inadequately controlled on metformin 500 mg bid monotherapy by showing that patients treated with the combination of vildagliptin 100 mg qd and metformin 500 mg bid have a superior GI tolerability compared to those treated with metformin up to 1000 mg bid over 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 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 closest prior measurement to Day 1 (including scheduled and unscheduled visits) if the Day 1 measurement was missing. | — |
Countries
Czech Republic, Germany, Hungary, Italy, United Kingdom
Outcome results
None listed