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, 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. 2. Patients with T2DM, diagnosed at least 6 weeks prior to visit 1, 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 at any time in the past for > 3 consecutive months. 3. Age = 18 years. 4. Body mass index (BMI) in the range of 22-35 kg/m2 inclusive at visit 1. 5. HbA1c = 7.5% at visit 1. 6. Agreement to maintain prior diet and exercise habits during the full course of the study. 7. Ability to comply with all study requirements and signed informed consent to participate in the study. 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). 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. • myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass surgery, unstable angina or stroke. 6. Congestive heart failure NYHA class III or IV. 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. 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. Insulin treatment within the past 6 months. 12. Treatment with growth hormone or similar drugs. 13. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1. 14. Treatment with class Ia, Ib and Ic or III anti-arrhythmics. 15. 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. 16. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e., cytostatic drugs). 17. Any of the following significant laboratory abnormalities. • ALT, AST greater than 3 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. • Clinically significant TSH outside of normal range at visit 1; thyroid hormone replacement is allowed if the dosage has been stable for at least 3 months. • Clinically significant laboratory abnormalities, confirmed by repeat measurement, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1. • Fasting triglycerides >700 mg/dL (> 7.9 mmol/L) at visit 1. 18. History of active substance abuse (including alcohol) within the past 2 years, potentially unreliable patients, and those judged by the investigator to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the effect of 4 week treatment with vildagliptin compared to placebo on the glucagon counterregulatory response to hypoglycemia in patients with T2DM, assessed as mean glucagon level (AUC / sampling period) of the last 30 min of the 2.5 mM hypoglycemic clamp step ;Secondary Objective: 1. To evaluate the effect of 4 week treatment with vildagliptin compared to placebo on the glucagon counterregulatory response to hypoglycemia in patients with T2DM, assessed as glucagon Cmax of the 2.5 mM hypoglycemic clamp step 2. To evaluate the effect of 4 week treatment with vildagliptin compared to placebo on the ‘insulin secretion rate (ISR) relative to glucose’ at the hypoglycemic clamp step in patients with T2DM. 3. To evaluate the effect of 4 week treatment with vildagliptin compared to placebo on HbA1c and fasting plasma glucose (FPG) in patients with T2DM. ;Primary end point(s): The assessment of the effect of 4 week treatment with vildagliptin compared to placebo on the glucagon counterregulatory response to hypoglycemia in patients with T2DM, assessed as mean glucagon level . The primary efficacy variable, mean plasma glucagon level of the last 30 minutes of the 2.5 mM hypoglycemic clamp test, is defined as the area under the 225-255 minutes prandial plasma glucagon curve (AUC225-255min) divided by the sampling period after 4 weeks of treatment. | — |
Countries
Sweden
Outcome results
None listed