Study of Efficacy and Safety of Vildagliptin as add-on Insulin Therapy in T2DM Patients

Study Overview
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Brief Summary
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The purpose of this study was to assess the efficacy and safety of vildagliptin 50 mg bid add-on therapy to improve overall glycemic control in patients with T2DM inadequately controlled by insulin, with or without concomitant metformin treatment. It was agreed with PMDA to conduct a postmarketing clinical trial to further collect the efficacy and safety data of vildagliptin especially in Japanese patients when it iwas used on top of insulin.

Official Title
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A 12-week, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Equa (Vildagliptin) 50 mg 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 (T2DM)

Intervention / Treatment
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* Drug: Vildagliptin (LAF237)
* Drug: Placebo
* Drug: Insulin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of T2DM by standard criteria. HbA1c ≥ 7.0 to ≤ 10% at Visit 1. Age: ≥ 20 to < 75 years old at Visit 1. BMI ≥ 20 to ≤ 35 kg/m2 at Visit 1. Exclusion Criteria: FPG ≥ 270 mg/dL (≥15 mmol/L) at Visit 1. Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes. Significant heart diseases Hepatic disorder Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vildagliptin (LAF237)<br>Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study | Drug: Vildagliptin (LAF237)<br>* Corresponds to vildagliptin (LAF237) 50 mg tablets twice daily<br>* Other names: Vildagliptin;Drug: Insulin<br>* Patients continued their prescribed insulin dose. The dose of insulin remained within a 10% increase of the baseline dose throughout the trial (with no change in frequency or insulin type) unless dose adjustments were required for safety reasons. The insulin dose was allowed to be decreased for safety reasons at anytime without specific dose limits at the Investigator's discretion.<br>Drug: Metformin<br>* Patients continued their prescribed metformin dose, if applicable.<br>|
| Placebo Comparator: Placebo<br>In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study | Drug: Placebo<br>* Matching placebo of vildagliptin 50 mg twice daily<br>Drug: Insulin<br>* Patients continued their prescribed insulin dose. The dose of insulin remained within a 10% increase of the baseline dose throughout the trial (with no change in frequency or insulin type) unless dose adjustments were required for safety reasons. The insulin dose was allowed to be decreased for safety reasons at anytime without specific dose limits at the Investigator's discretion.<br>Drug: Metformin<br>* Patients continued their prescribed metformin dose, if applicable.<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 12 Weeks Between Treatment Groups | HbA1c was performed on a blood sample obtained and measured by high performance liquid chromatography performed at a central laboratory. | Baseline, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Meeting Responder Rates in HbA1c | Responder rate was analyzed in categories: Criterion 1- Endpoint HbA1c ≤ 6.5%, Criterion 2- Endpoint HbA1c < 7% , Criterion 3- Endpoint HbA1c < 7% in patients with baseline HbA1c ≤ 8%, Criterion 4- HbA1c reduction from baseline at endpoint ≥ 1%, Criterion 5- HbA1c reduction from baseline at endpoint ≥ 0.5%. The number of patients analyzed for Criterion 1 and 2 include only patients with baseline HbA1c ≥ 7% (> 6.5%) and endpoint HbA1c measurement. The number of patients analyzed for Criterion 3 includes only patients with 7% ≤ baseline HbA1c ≤ 8% and endpoint HbA1c measurement. The number of patients analyzed for Criterion 4 and 5 include patients with both baseline and endpoint HbA1c measurements. | Baseline, week 12 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at 12 Weeks | FPG was performed on a blood sample obtained and analyzed at a central laboratory. | Baseline, week 12 | 
| Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | Hypoglycemic events are defined as a) symptoms suggestive of hypoglycemia, where the patient is able to initiate self-treatment and plasma glucose measurement is < 56 mg/dL (grade 1), b) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and plasma glucose measurement is < 56 mg/dL (grade 2), c) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and no plasma glucose measurement is available (suspected grade 2) | 12 weeks | 
| Number of Participants With Adverse Events, Serious Adverse Events and Death | The occurrence of adverse events was sought by non-directive questioning of the patient at each visit. Adverse events are defined as appearance or worsening of any undesirable symptom, vital sign, or medical conditions. 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. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus (DM) ,, diabetes,, noninsulin-dependent diabetes mellitus (NIDDM),, adult-onset diabetes,, high blood sugar,, T2DM