Effect of 13-Week Treatment With Vildagliptin as Add-On Therapy to Improve Glucose Variability in Type II Diabetes

Study Overview
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Brief Summary
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The purpose of the study is to assess if the addition of vildagliptin as add-on therapy improves glucose variability in type 2 diabetes mellitus (T2DM) patients inadequately controlled with insulin, with special emphasis in hypoglycemic episodes measured by continuous glucose monitoring.

Official Title
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A Multicenter, Double-Blind, Randomized, Parallel-Group Placebo-Controlled Study to Compare the Effect of 13-Week Treatment With Vildagliptin as Add-On Therapy to Improve Glucose Variability in Type 2 Diabetes Mellitus Patients Inadequately Controlled With Insulin.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Vildagliptin
* Drug: Insulin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent read and signed before any protocol procedure. Free will to sign the informed consent. Male and female between 18 and 80 years. If female, patient must be non-fertile or of childbearing potential using a medically approved birth control method. Type 2 diabetes mellitus Patient under insulin treatment within 3 years with stable insulin NPH (Neutral ProtamineHagedorn) regimen at dose of at least 20 UI/day up to 40 UI/day for a minimum of 4 weeks prior to enrolment, only NPH and glargine insulin are allowed. HbA1c between 7.5 to 9%. Fasting plasma glucose (FPG) less than 270 mg/dL. Body mass index (BMI) between 20 to 35 kg/m2. Free willing to take the vildagliptin tablets during the study. Exclusion Criteria Pregnant or lactating female or without birth control method if of childbearing potential. Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing's syndrome. Acute cardiovascular complications or metabolic complications within the past 4 months. History cerebrovascular disease during the last year. History of Torsades de Points, ventricular tachycardia or ventricular fibrillation. Ischemic heart disease (e.g. myocardial infarction, unstable angina, coronary artery bypass surgery). Congestive heart failure requiring pharmacologic treatment. Any known serious heart condition. ALT and/or AST greater than three times the upper limit of the normal range. Serum creatinine levels greater than 1.5 mg/dL Malignancy including leukemia and lymphoma within the last 5 years Other inlcusion/exclusion 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>Vildagliptin 50 mg twice daily (bid) + Insulin 20 to 40 IU/day | Drug: Vildagliptin<br>* Orally active and highly selective inhibitor of DPP-4<br>Drug: Insulin<br>* Long- acting human insulin analog indicated to improve glycemic control<br>|
| Placebo Comparator: Placebo<br>Insulin 20 to 40 IU/day + Vildagliptin Placebo twice daily (bid) | Drug: Insulin<br>* Long- acting human insulin analog indicated to improve glycemic control<br>Drug: Placebo<br>* Matching placebo of vildagliptin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with hyperglycemic events evaluated with CGM | An hypoglycemic event is defined as any continuous glucose monitoring (CGM) measurement less than 60 mg/dL and a hyperglycemic is define as any CGM greater than 140 mg/dL. | At 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hypoglycemia and/or hyperglycemia measured by CGM | An episode of hypoglycemia is defined as any value of glucose under 60 mg/dL, an episode of hyperglycemia is defined as any value of glucose above 140mg/dL measured by CGM. | 13 weeks | 
| Area under the curve (AUC 0-24) of the excursions of glucose values below 60 mg/dl per day | Duration and intensity of hypoglycemic episodes, measured as area under the curve (AUC 0-24) of the excursions of glucose values below 60 mg/dl per day, measured by continuous glucose monitoring | 0 to 24 hours daily for week 1, 4 and 13 | 
| Average of insulin units per day administered during the study | Change from baseline | 13 weeks | 
| Changes from the baseline in Lipid Profile | Lipid Profile will include total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol | Baseline, 13 weeks | 
| Change from baseline in Body weight | Weight will be measured on Kg. | Baseline, 13 weeks | 
| Change from baseline in Blood pressure (BP), | BP will be mesured on mmHg | Baseline, 13 weeks | 
| Change from baseline in Fasting plasma glucose (FPG), | FPG will be measured on mg/dL | Baseline, 13 weeks | 
| Change from baseline in Hemoglobin A1C (HbA1c) | HbA1c will be measured on % | Baseline, 13 weeks | 
| Change from baseline in Creatinine | Creatinine will be measured on mg/dL | Baseline, 13 weeks | 
| Change from baseline in C-peptide | C-Peptide will be measured on microIU/mL | Baseline, 13 weeks | 
| Changes from baseline in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) | ALT/AST will be measured on ratio. | Baseline, 13 week | 
| Changes from baseline in Direct bilirubin | Bilirubin will be measure on mg/dL | Baseline, 13 weeks | 
| Changes from baseline in Body Mass Index (BMI) |  | Baseline, 13 weeks | 
| Number of patients with adverse events, serious adverse events and death as evaluation of safety and tolerability of coadministration of vildagliptin with insulin |  | 13 weeks | 

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