Vildagliptin vs Sitagliptin add-on to Insulin - Impact on Glycemic Profile and Correlation of Hypoglycemic Episodes and Heart Function

Launched by NOVARTIS PHARMACEUTICALS · Sep 13, 2012

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Eligibility criteria

• Inclusion Criteria:
• • 1. Written informed consent must be obtained before any assessment is performed.
• • 2. Ability to comply with all study requirements. 3. Patients with Type 2 diabetes treated with stable, once or twice daily doses (minimal dose of 0.3 unit/kg/day) of basal long-acting or intermediate-acting insulin alone or in pre-mixed combination with rapid-acting or short-acting insulin for at least 12 weeks prior to Visit 1. Stable is defined as ±10% of the Visit 1 dose during the previous 12 weeks.
• • 4. Patients receiving metformin must be on a stable dose of metformin (at least 1500 mg daily or a maximally tolerated dose) for at least 12 weeks prior to Visit 1. 5. HbA1c ≥7.5 to ≤ 9,0% at Visit 1 6. Known CV disease based on a documented history of one or more of pre-defined criteria 7. Age: ≥40 to ≤80 years at Visit 1
• Exclusion Criteria:
• * 1. FPG ≥ 270 mg/dL (15 mmol/L) at Visit 1. 2. Use of any of the following medications as assessed at Visit 1:
• • 1. rapid or short acting insulin except in pre-mixed formulations with intermediate or long-acting insulin; insulin administration more frequently than twice-daily, or total insulin dose \< 0.3 unit/kg/day for the past 12 weeks
• • 2. use of any oral antidiabetic medication or GLP-1 analogues within the last 12 weeks, except metformin
• • 3. use of weight control products including weight-loss medications in the last 12 weeks.
• • 4. use of oral (≥7 consecutive days) or chronic parenteral or intra-articular corticosteroid treatment within the last 8 weeks. Inhaled or topical steroids without systemic effects will be allowed.
• • 5. treatment with growth hormone within the previous 6 months.
• • 6. treatment with any drug of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study.
• 3. a history or evidence of any of the following at Visit 1:
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• • 1. acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including precoma and coma) within the past 6 months.
• • 2. current diagnosis of congestive heart failure (NYHA III or IV).
• • 3. myocardial infarction within the past 6 months.
• • 4. coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months.
• • 5. Stroke, transient ischemic attack, or reversible ischemic neurologic deficit within the past 6 months.
• • 6. unstable angina within the past 6 months.
• • 7. sustained and clinically relevant ventricular arrhythmia (patients with premature ventricular contractions if deemed not clinically significant may be enrolled).
• • 8. Patients with permanent atrial fibrillation or pacemaker.
• • 9. active substance abuse, alcohol abuse and history of alcohol-related diseases within the past 2 years.
• • 10. type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing's syndrome or acromegaly-associated diabetes).
• • 11. malignancy of an organ system (other than localized basal cell carcinoma of the skin) treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• 12. hepatic disorder defined as:
• • acute or chronic liver disease, evidence of hepatitis, cirrhosis or portal hypertension.
• • history of imaging abnormalities that suggest liver disease (except hepatic steatosis), such as portal hypertension, capsule scalloping, cirrhosis.
• • 13. acute infections which may affect blood glucose control within the past 4 weeks.
• 4. any of the following significant laboratory abnormalities as assessed at Visit 1:
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• • 1. clinically significant increase or reduction in thyroid stimulating hormone (TSH) outside of the normal range.
• • 2. clinically significant renal dysfunction: glomerular filtration rate (GFR) \<50 mL/min/1.73m2 (via MDRD formula).
• • 3. Patients on metformin with a GFR \<60 mL/min/1.73m2 (via MDRD formula).
• • 4. alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2 x upper limit of normal (ULN) at Visit 1, confirmed by repeated measurements within 3 working days.
• • 5. total bilirubin \> 2 x ULN and/or direct bilirubin \> 1 x ULN confirmed by repeated measurements within 3 working days.
• • 6. positive Hepatitis B surface antigen (HBsAg).
• • 7. positive Hepatitis C virus (HCV) antibody test (anti-HCV).
• • 8. elevated fasting triglycerides (TGs) \> 500mg/dL (5.65mmol/L), confirmed by a repeated measurements within 3 working days.
• • 9. clinically significant laboratory abnormalities which, in the opinion of the investigator, cause the patient to be considered inappropriate for inclusion in the study.
• 5. any of the following electrocardiographic abnormalities at Visit 1:
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• • 1. second or third degree atrio-ventricular block.
• • 2. A QTc of \> 440 ms.
• • 3. clinically significant electrocardiogram (ECG) abnormalities which, in the opinion of the investigator, may cause the patient to be considered inappropriate for inclusion in the study
• • Other protocol-defined inclusion/exclusion criteria may apply.