Oral Combination of Glimepiride/Vildagliptin/Metformin in Patients With T2D and Dual Treatment Failure

Study Overview
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Brief Summary
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Phase IIIb, randomized, multicenter, double-blind, prospective study to evaluate the efficacy and safety of a daily fixed-dose combination of glimepiride / vildagliptin / metformin in patients with type 2 diabetes with a history of dual treatment failure and combined or individual oral antidiabetics with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4 or Biguanide / iDPP4. To evaluate the changes in the percentage of HbA1c at 3 and 6 months with regard to their baseline measurement.

Detailed Description
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To achieve glycemic control goals, a combination of medications with complementary mechanisms of action, with fasting and postprandial effects, may be required to achieve and maintain clinically acceptable glycemic control in some patients. A fixed combination of two or more therapeutic agents with complementary mechanisms of action makes it possible to optimize compliance and adherence to treatment among patients with T2D because it is administered once a day with the same efficacy of the separate components, but with fewer gastrointestinal effects. This is reflected in a reduction in HA1c and a lower evolution to long-term complications of T2D. Phase IIIb, randomized, multicenter, double-blind, prospective study to evaluate the efficacy and safety of a daily fixed-dose combination of glimepiride / vildagliptin / metformin in patients with type 2 diabetes with a history of dual treatment failure and combined or individual oral antidiabetics with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4 or Biguanide / iDPP4.

Official Title
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Efficacy and Safety of the Oral Combined Therapy Glimepiride / Vildagliptin / Metformin in Patients With Type 2 Diabetes With Dual Treatment Failure

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: A1=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)
* Drug: B2=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)
* Drug: (A2) Glimepiride/Vildagliptin/Metformin
* Drug: (B2) Glimepiride/Vildagliptin/Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female. Age >18 years old at the beginning of the study. Diagnosis of type 2 diabetes prior to the start of the study. Therapeutic failure to a dual treatment with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4, Biguanide / iDPP4. HbA1c ≥ 7.5% and ≤ 11% during screening tests. Women of childbearing potential using a contraceptive method (barrier, oral hormonal, injectable, subdermal) or naturally or surgically sterile in menopause. Subject agree to participate in the study and give informed consent in writing. Exclusion Criteria: The drug is contraindicated for medical reasons. History of Type 1 Diabetes Mellitus. History of metabolic complications such as ketoacidosis or nonketotic hyperosmolar state. History of gastric bariatric surgery or gastric band in the last year. History of drug or alcohol abuse in the past year. Body Mass Index <20 kg/m2 and >40 kg/m2. Acute or severe renal dysfunction (glomerular filtration <30 ml / min / 1.72 m2). History of chronic liver disease or ALT and / or AST ≥3 times the normal upper limit and / or Total Bilirubin> 2.5 times the upper limit of normal, or GGT ≥3 times the upper limit of normal. Pregnant and / or lactating women. The patient is participating in another clinical study involving an investigational treatment or participated in one in the previous 4 weeks. At medical criteria, a disease that affects the prognosis and prevents outpatient management, for example, but not restricted to: end-stage cancer, kidney, heart, respiratory or liver failure, mental illness, with scheduled surgical or hospital procedures. Be a patient with a working relationship with the main researcher or the research center or deprived of liberty.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Group A1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg).<br>Tablets, orally, once a day. Initial dose for the first 45 days of intervention. | Drug: A1=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)<br>* Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Initial dose for the first 45 days of intervention.<br>* Other names: (A1) Glimepiride/Vildagliptin/Metformin;|
| Experimental: Group B1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg)<br>Tablets, orally, once a day. Initial dose for the first 45 days of intervention. | Drug: B2=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)<br>* take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Initial dose for the first 45 days of intervention.<br>* Other names: (B1) Glimepiride/Vildagliptin/Metformin;|
| Experimental: Group A2: Glimepiride (2mg) / Vildagliptin (50mg) / Metformin (1000mg)<br>Tablets, orally, once a day. Dose escalation if the patients meets established criteria. | Drug: (A2) Glimepiride/Vildagliptin/Metformin<br>* Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Escalation dose in cause the patient meets established criteria.<br>* Other names: A2=Glimepiride / Vildagliptin / Metformin (2 mg/ 50 mg/ 1000 mg);|
| Experimental: Group B2: Glimepiride (4mg) / Vildagliptin (50mg) / Metformin (1000mg)<br>Tablets, orally, once a day. Dose escalation if the patients meets established criteria. | Drug: (B2) Glimepiride/Vildagliptin/Metformin<br>* Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Escalation dose in cause the patient meets established criteria.<br>* Other names: B2=Glimepiride / Vildagliptin / Metformin (4 mg/ 50 mg/ 1000 mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare changes in HbA1 | Mean change in HbA1c | baseline, 3 and 6 months of treatment | 
| Proportion of patients who change their HbA1c concentration | Proportion of patients who change their HbA1c by at least 1 percent | baseline, 3 and 6 months of treatment | 
| Mean difference change between groups in HbA1c concentration | Difference greater than 0.3 between group A and B HbA1c concentration | baseline, 3 and 6 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean glucose change | Compare changes in glucose between baseline, 3 and 6 months of treatment | baseline, 3 and 6 months of treatment | 
| Incidence of adverse events and reactions | Description of al the adverse events and reactions presented during the study | baseline, 3 and 6 months of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, Combine therapy, Hypoglycemic agents