type-2 diabetes mellitus with pre-existing cardiovascular disease MedDRA version: 14.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Galvus
Pharmaceutical Form: Tablet
INN or Proposed INN: VILDAGLIPTIN
CAS Number: 274901-16-5
Current Sponsor code: LAF237
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion 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 the following at screening: o Acute coronary syndrome or MI (at least 6 months before V1) o Stroke/TIA (at least 6 months before V1) o PCI/CABG (at least 6 months before V1) o Heart failure NYHA I/II o Coronary heart disease, diagnosis by coronarogram o >75% Stenosis of the internal carotid artery, diagnosed by Doppler sonography o Peripheral arterial disease (Fontaine stage 2) 7. Age: =40 to =80 years at Visit 1 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
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: a. 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 b. use of any oral antidiabetic medication or GLP-1 analogues within the last 12 weeks, except metformin c. use of weight control products including weight-loss medications in the last 12 weeks. d. 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. e. treatment with growth hormone within the previous 6 months. f. 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: a. acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including precoma and coma) within the past 6 months. b. current diagnosis of congestive heart failure (NYHA III or IV). c. myocardial infarction within the past 6 months. d. coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months. e. Stroke, transient ischemic attack, or reversible ischemic neurologic deficit within the past 6 months. f. unstable angina within the past 6 months. g. sustained and clinically relevant ventricular arrhythmia (patients with premature ventricular contractions if deemed not clinically significant may be enrolled). h. Patients with permanent atrial fibrillation or pacemaker. i. active substance abuse, alcohol abuse and history of alcohol-related diseases within the past 2 years. j. type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing’s syndrome or acromegaly-associated diabetes). k. malignancy of an organ system l. hepatic disorder m. acute infections which may affect blood glucose control within the past 4 weeks. 4. significant laboratory abnormalities 5. electrocardiographic abnormalities 6. previous or current participation in any vildagliptin clinical study (except CLAF237A23135 [vildagliptin add-on-insulin trial]). 7. concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study. 8. donation of blood or significant blood loss equaling to at least one unit of blood (500 mL) within the past 2 weeks before screening or a blood transfusion within the past 12 weeks before screening or planned regular transfusions during the study period. 9. potentially unreliable, inability to comply with the study procedures or medications, and/or judged by the investigator to be unsuitable for the study. 10. use of an investigative drug within 30 days or 5 half-lives of the drug before screening, whichever is longer. 11. Known sensitivity to study drug(s) or class of study drug(s) 12. Allergies or intolerance against test meal components; vegetarians. 13. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study 14. Study personnel or first degree relatives of investigator(s) must not be included in the study. 15. Women o who are pregnant or breast feeding o who are menstr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that vildagliptin leads to a favorable hypoglycemic profile compared to sitagliptin, after 8 weeks of treatment, each, when used in combination with insulin. The hypoglycemic profile will be defined as the area under the glucose-time profile obtained by a 5 day-continuous glucose monitoring where the glucose levels are lower than the hypoglycemia threshold of 70 mg/dL. ;Secondary Objective: 1. To evaluate whether vildagliptin leads to a lower number of hypoglycemic events. compared to sitagliptin, when used in combination with insulin. 2. To evaluate by CGM measurement whether vildagliptin leads to a shorter mean duration of hypoglycemic events compared to sitagliptin, when used in combination with insulin. 3. To evaluate by CGM measurement the grade of severity of hypoglycemia measured as the mean amplitude. 4. To evaluate whether vildagliptin leads to a lower number of severe hypoglycemic events compared to sitagliptin, when used in combination with insulin. 5. To evaluate whether vildagliptin leads to less glucose fluctuations during the day. 6. To evaluate if hypoglycemic events increases the risk of ECG abnormalities 7. To evaluate whether treatment with vildagliptin results in lower levels of pro-inflammatory biomarkers (hsCRP, IL-6). 8. To evaluate whether treatment with vildagliptin results in lower pro-insulin/C-Peptide ratio. ;Primary end point(s): The primary variable is the hypoglycemia profile computed as the area under the glucose-time profile where the glucose levels are lower than the hypoglycemia threshold of 70 mg/dl. This area seems to be a sensitive measure to summarize the frequency, the severity and the duration of hypoglycemia. The area will be computed from the data of the CGMS iPro2 Continuous Glucose Recorder collected during 5 days.;Timepoint(s) of evaluation of this end point: after 8 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The number of (severe) hypoglycemic events will be compared between treatment groups using a negative binomial regression model with factors patient and treatment. Rate ratios and their confidence intervals will be computed. The duration of hypoglycemia and the glucose fluctuations (MAGE) will be analyzed analogously to the primary endpoint using ANOVA. For calculating MAGE the average interstitial glucose level and its standard deviation (SD) measured at visits 2.3, 3.3 and 5.3 will be calculated from all of the available glucose measurements made during CGM. The mean amplitude of glycemic excursion over 24 hours (MAGE) was designed to quantify major excursions of glycemia but exclude minor oscillations. Therefore only changes greater than 1 SD of average interstitial glucose level will be included in the calculation. MAGE will be calculated as the arithmetic mean of all differences between consecutive peaks and valleys or valley – peak direction (Service et al., 1070). Peaks (valleys) are defined as interstitial glucose values preceded and followed by an increase (decrease) and decrease (increase), respectively. ;Timepoint(s) of evaluation of this end point: after 8 weeks of treatment | — |
Countries
Germany
Contacts
Public ContactMedizinischer Infoservice
Novartis Pharma GmbH
Outcome results
None listed