Efficacy and Safety of Vildagliptin 50mg Bid as an add-on Therapy to Insulin With or Without Metformin, in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of vildagliptin 50mg bid add-on therapy to improve overall glycemic control in patients with type 2 diabetes mellitus inadequately controlled on insulin with or without metformin treatment.

Official Title
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A 24-week, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Vildagliptin 50mg Bid as an add-on Therapy to Insulin, With or Without Metformin, in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Vildagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with confirmed diagnosis of Type2 diabetes mellitus (T2DM) by standard criteria C-peptide >0.6 ng/ml (>0.20 nmol/L). HbA1c ≥7.5 to ≤11% at Visit 1 Treatment with stable, once or twice daily doses (maximum dose of < 1 unit/kg/day) of basal (long-acting, intermediate-acting) insulin alone or pre-mixed 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 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 Body Mass Index (BMI) ≥20 to ≤40 kg/m2 at Visit Exclusion Criteria: Patients fulfilling any of the following criteria are not eligible for participation in the study Fasting plasma glucose (FPG) ≥240 mg/dl (13.3 mmol/L) at Visit 1 Pregnant or lactating women Acute metabolic diabetes complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months Current diagnosis of congestive heart failure (NYHA III or IV). Myocardial infarction (MI) within the past 6 months Liver disease such as cirrhosis or chronic active hepatitis Other protocol defined inclusion/excusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vildagliptin<br>Eligible patients will receive vildagliptin 50 mg in addition to their stable dose of insulin with or without metformin. One tablet should be taken twice daily as one tablet before breakfast meal and one tablet before the evening meal for 24 weeks. | Drug: Vildagliptin<br>* Patient will receive vildagliptin 50mg twice daily (bid) in addition to their stable dose of insulin with or without metformin for 24 weeks<br>* Other names: Galvus, LAF237;|
| Placebo Comparator: Placebo<br>Eligible patients will receive matching placebo in addition to their stable dose of insulin with or without metformin. One tablet should be taken twice daily as one tablet before breakfast meal and one tablet before the evening meal for 24 weeks. | Drug: Placebo<br>* Patient will receive matching placebo to vildagliptin in addition to their stable dose of insulin with or without metformin for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glycosylated hemoglobin (HbA1c) at study endpoint, assessed in overall study population | HbA1c analysis will be performed on a blood sample obtained by study personnel at every visit and measured by ion exchange HPLC. Study endpoint is defined as final available post- randomization assessment obtained at any visit prior to or at the start of major change in insulin use, up to final scheduled study visit (week 24 visit) inclusive. | Baseline and every study visit up to 24 weeks | 
| Change from baseline in glycosylated hemoglobin (HbA1c) at study endpoint, assessed in Chinese study population | HbA1c analysis will be performed on a blood sample obtained by study personnel at every visit and measured by ion exchange HPLC. Study endpoint is defined as final available post- randomization assessment obtained at any visit prior to or at the start of major change in insulin use, up to final scheduled study visit (week 24 visit) inclusive. | Baseline and every study visit up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events, serious adverse events and death on over all population | Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards. | 24 weeks | 
| Change from baseline after 24 weeks of treatment in fasting plasma glucose (FPG)on overall population | FPG will be performed on the blood samples collected at all every study visits from baseline to week 24. | Baseline, week 24 | 
| Percentage of patients meeting responder criteria after 24 weeks treatment on overall population | Responder rate will be analyzed in the following categories: Endpoint HbA1c ≤ 6.5% Endpoint HbA1c < 7% Endpoint HbA1c <7% in patients with baseline HbA1c ≤ 8% The percentage of patients meeting each of the responder criteria as described, as well as the percentage of patients meeting any of these criteria in each treatment group will be computed | After 24 weeks | 
| Number of patients with adverse events, serious adverse events and death on Chinese population | Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards. | 24 weeks | 
| Change from baseline after 24 weeks of treatment in fasting plasma glucose (FPG) on Chinese population | FPG will be performed on the blood samples collected at all every study visits from baseline to week 24. | Baseline, week 24 | 
| Percentage of patients meeting responder criteria after 24 weeks treatment on Chinese population | Responder rate will be analyzed in the following categories: • Endpoint HbA1c ≤ 6.5% • Endpoint HbA1c < 7% • Endpoint HbA1c <7% in patients with baseline HbA1c ≤ 8% The percentage of patients meeting each of the responder criteria as described, as well as the percentage of patients meeting any of these criteria in each treatment group will be computed | After 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Vildagliptin