Type II Diabetes
Conditions
Interventions
Product Name: LAF237
Pharmaceutical Form: Tablet
INN or Proposed INN: Vildagliptin
Current Sponsor code: LAF237
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Sponsors
Novartis Sverige AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male, non-fertile female (i.e., post menopausal, post hysterectomy, or sterilized by tubal ligation) or female of childbearing potential using a non-hormonal medically approved birth control method (e.g., IUD, double-barrier contraception). Females using hormonal contraceptives must use a non-hormonal medically approved birth control method in addition during the full course of the study. A female of childbearing potential must be willing to use the same method(s) of contraception during the entire study. 2. Drug naïve patients with type 2 diabetes (drug naïve patients are defined as patients who have had no treatment with oral antidiabetic agents for at least 12 weeks prior to study entry (visit 1) and no treatment with oral antidiabetic agents for > 3 consecutive months at any time in the past). 3. Age in the range of 18 to 80 years inclusive. 4. Body mass index (BMI) in the range of 22-45 kg/m2 inclusive at visit 1. 5. HbA1c in the range of 7.5 to 11% inclusive at visit 1. 6. FPG ? 270 mg/dL (15 mmol/L) at visit 1. 7. Agreement to maintain prior diet and exercise habits during the full course of the study. 8. Written informed consent to participate in the study. 9. Ability to comply with all study requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=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 the 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; or unstable angina 6. Congestive heart failure. 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. Acromegaly or treatment with growth hormone or similar drugs. 11. Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study. 12. 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. 13. Contraindications and warnings according to the country specific label for rosiglitazone not listed in the other exclusion criteria. 14. Known sensitivity to rosiglitazone, pioglitazone or similar drugs. 15. Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months. 16. Chronic oral or parenteral corticosteroid treatment (> 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. Thyroid hormone replacement is allowed if the dosage has been stable for at least 3 months and the TSH is within normal limits at visit 1. 19. Investigational drug treatment within 4 weeks prior to Visit 1 unless local health authority guidelines mandate a longer period. 20. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e., cytostatic drugs). 21. 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 > 2.5 mg/dL (220 ?mol/L) at visit 1. • TSH outside normal range at visit 1. • Clinically significant laboratory abnormalities, confirmed by repeat measurement, that may interfere with the assessment of safety and/or efficacy of the study drug, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1. • Fasting triglycerides ?700 mg/dL (>7.9 mmol/l) at visit 1. • Positive GAD antibodies at visit 1. (GAD antibodies will be tested in patients < 30 years.) 22. History of active substance abuse (including alcohol) within the past 2 years. 23
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To demonstrate the efficacy of LAF237 in patients with type 2 diabetes by testing the hypothesis that the hemoglobin A1c (HbA1c) reduction with LAF237 is not inferior to that with rosiglitazone after 24 weeks of treatment.;Secondary Objective: 1. To demonstrate the efficacy of LAF237 in patients with type 2 diabetes by testing the hypothesis that the fasting plasma glucose (FPG) reduction with LAF237 is not inferior to that with rosiglitazone after 24 weeks of treatment. 2. To demonstrate the safety of LAF237 in patients with type 2 diabetes by showing that LAF237 has a similar adverse event profile compared to rosiglitazone after 24 weeks of treatment. 3. To demonstrate the efficacy of LAF237 in patients with type 2 diabetes by showing that the initial responder rates (see Section 7.4 for definitions) with LAF237 are not less than those with rosiglitazone after 24 weeks of treatment. 4. To demonstrate the efficacy of LAF237 in patients with type 2 diabetes by showing that the responder rate (defined as an absolute reduction in HbA1c of = 0.7%) with LAF237 is greater than that with rosiglitazone after 12 weeks of treatment. ;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 screening measurement (Week 2, Visit 1) if Day 1 measurement is missing. | — |
Countries
Sweden
Outcome results
None listed