Phase 3 Study to Compare the Efficacy and Safety of Gemigliptin and Vildagliptin as Add-on Therapy to Metformin in People With Type 2 Diabetes Inadequately Controlled With Metformin

Study Overview
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Brief Summary
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Primary Objective: To compare the clinical efficacy of gemigliptin and vildagliptin as add-on therapy to metformin in terms of change in Hemoglobin A1c (HbA1c) reduction. Secondary Objectives: To compare the safety and tolerability of gemigliptin and vildagliptin: Number of patients who experience at least one episode of hypoglycemia. Number of patients experiencing adverse event (AE), serious adverse event (SAE). Assessment of patients compliance defined as number tablets returned by patients.

Detailed Description
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The study consists of 2 weeks screening and 24 weeks of treatment (a total of 26 weeks). The protocol includes a screening period of two weeks, after which they will be randomized to receive gemigliptin or vildagliptin. Patients will be evaluated through 4 mandatory visits during the study. Visit 1: Week -2 (screening) Visit 2: Week 0 (randomization) Visit 3: Week 12 (efficacy and safety evaluation) Visit 4: Week 24 (efficacy and safety evaluation)

Official Title
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A Multicentre, National, Randomized, Parallel-group, Phase 3 Study to Compare the Efficacy and Safety of Gemigliptin and Vildagliptin as Add-on Therapy to Metformin in People With Type 2 Diabetes Inadequately Controlled With Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: GEMIGLIPTIN LS15-0444
* Drug: vildagliptin
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with Type 2 diabetes mellitus. Patients inadequately controlled with metformin at the maximal effective and tolerated dose of metformin for at least 12 weeks or who are on a stable dose of ≥1500 mg daily for a minimum of ≥4 weeks prior to study entry. Signed informed consent obtained prior to any study procedures. Exclusion criteria: Patients with type 1 diabetes mellitus, gestational diabetes, or diabetes secondary to pancreatic disorders, drug or chemical agent intake. Male and female younger than 18 and older than 75 years old. Patients with HbA1c ≤7% and ≥9.5%. Patients with 20 kg/m^2 > body mass index (BMI) >40 kg/m^2. Patients with history of hypersensitivity to metformin. Patients with history of hypersensitivity to vildagliptin. Lactose intolerance, lactase deficit, glucose-galactose malabsorption. Patients who have a history of acute metabolic complications such as lactic acidosis, diabetic pre-coma, diabetic ketoacidosis or hyperosmolar hyperglycemic state within 3 months before study entry. Patients who were treated with insulin or glucagon-like peptide-1 (GLP-1) analogue. Patients who have been treated by thiazolidinediones (pioglitazone) in the last 6 months. Use of systemic glucocorticosteroids (excluding topical application or inhaled forms) for 7 consecutive days or within more than 3 months prior to study entry. Patients with impaired hepatic function (alanine transaminase [ALT], aspartate transaminase [AST] activity >1.5 times the upper limit of normal [ULN]). Patients with impaired renal function (serum creatinine concentration >135ɥmol/l in men and >110ɥmol/l in female). Patients who had experienced myocardial infarction, stroke, unstable angina or coronary artery bypass surgery within 6 months prior to screening, or patients with arrhythmia requiring treatment. Patients with chronic heart failure II-IV functional class according to the classification of NYHA (New York Heart Association). Patients taking medicines of thyroid hormones, warfarin, dicoumarin or digoxin. Patients who took sodium channel blockers and SGLT2 inhibitors (or inhibitors sodium glucose transporters 2) in the last 6 weeks prior to study entry. Known history of alcohol or drug abuse within 6 months prior to screening. Pregnant or woman during breast feeding period. Women of childbearing potential not protected by effective contraceptive method of birth control. Men whose partners are planning pregnancy. History of hypersensitivity to the study drug or to a drug with a similar chemical structure. Use of any investigational drug within 3 months prior to study entry. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemigliptin<br>GEMIGLIPTIN LS15-0444 administered once a day for 24 weeks as add-on therapy to metformin | Drug: GEMIGLIPTIN LS15-0444<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: Zemiglo;Drug: metformin<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Active Comparator: Vildagliptin<br>Vildagliptin administered twice a day for 24 weeks as add-on therapy to metformin | Drug: vildagliptin<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: Galvus;Drug: metformin<br>* Pharmaceutical form:tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c |  | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting plasma glucose |  | Up to Week 24 | 
| Change from baseline in postprandial glucose |  | Up to Week 24 | 
| Percentage of patients achieving HbA1c <7% and <6.5% |  | Up to Week 24 | 
| Percentage of patients with at least one episode of hypoglycemia |  | Up to Week 24 | 
| Number of episode of hypoglycemia (symptomatic, asymptomatic, severe hypoglycemia) |  | Up to Week 24 | 
| Change from baseline in body weight |  | Up to Week 24 | 
| Number of adverse events |  | Up to Week 24 | 
| Number of serious adverse events |  | Up to Week 24 |