Efficacy and Safety of Gosogliptin as Monotherapy and in Combination With Metformin vs. Vildagliptin as Monotherapy and in Combination With Metformin in Drug-naive Type 2 Diabetic Patients.

Study Overview
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Brief Summary
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To demonstrate that efficacy of Gosogliptin as Monotherapy and in Combination with Metformin is non-inferior to efficacy of Vildagliptin as Monotherapy and in combination with Metformin in the effects on glycosilated hemoglobin (HbA1c) at Week 12 and Week 36 compared to baseline (Week 0).

Detailed Description
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Screening of patients at Week -2 Training for all complying patients in Diabetes Program School at Week -1 with glucometer and patient diary distribution for SMBG Randomization in one of two groups in the ratio 1:1. The 1st stage includes 12 weeks of monotherapy with Gosogliptin or Vildagliptin. The 2nd stage includes 24 weeks of combination therapy with Gosogliptin and Metformin or Vildagliptin and Metformin. Follow-up period of 4 weeks.

Official Title
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Evaluate Efficacy and Safety of Gosogliptin as Monotherapy and in Combination With Metformin vs. Vildagliptin as Monotherapy and in Combination With Metformin in Drug-naive Type 2 Diabetic Patients.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Gosogliptin
* Drug: Vildagliptin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women from 18 through 78 years Confirmed clinical diagnosis of type 2 diabetes mellitus Drug-naive patients or patients without hypoglycemic drug treatment at least till 12 weeks before screening Patient's agreed to use adequate methods of contraception during the study Body mass index 22-40 kg/m2 HbA1c 7.5 - 11.0% FPG < 15 mmol/L Signed informed consent Patient's ability to follow all protocol requirements Exclusion Criteria: Pregnancy and lactation, women who plan to become pregnant during the clinical study, women of child-bearing potential (i.e. non-stylized surgically and in period of post menopause less than 2 years) without adequate methods of contraception. History of type 1 diabetes mellitus and other forms Severe metabolic complications of diabetes as ketoacidosis, hyperosmolar coma during 6 weeks before screening Severe complication of diabetes, for instance proliferative retinopathy in active stage, autonomic neuropathy or gastroparesis A known allergy, hypersensitivity or contraindications to Gosogliptin, Vildagliptin, Metformin or their components Convulsive disorder; system autoimmune diseases or vascular collagenosis demanding the previous or current treatment by systemic corticosteroids, cytostatics; malignancy within the last 5 years (except for a basal-cell carcinoma); Significant cardiovascular diseases within 12 months of screening including: chronic heart failure of a class III or IV (NYHA), severe arrhythmia demanding treatment with antiarrhythmics, unstable angina, myocardial infarction, heart and coronary vessels surgery, heart valves diseases, transitory ischaemic attack or stroke, uncontrolled arterial hypertension with systolic Blood Pressure > 180 mm Hg and diastolic Blood Pressure > 110 mm Hg, pulmonary embolism or deep venous thrombosis A nephrotic syndrome, a chronic renal failure, serum creatinine > 1.5 mg/dL (132 µmol/L) in men and > 1.4 mg/dL (123 µmol/L) in women or GFR <60 ml/min/1.73m2 HBV, HCV or a liver cirrhosis; AST or ALT > 3 ULN; total bilirubin > 2 ULN HIV; severe infection that can affect glycemia within 30 days of screening Anemia (Hb ≤10.5 g/dL in women or ≤11.5 g/dL in men); loss of > 1 unit of blood ( 500 mL) or blood transfusion within 12 weeks of screening Drugs or alcohol abuse Administration of any study drug within 30 days of screening Inability to read or write; unwillingness to understand and follow the protocol procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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: Gosogliptin treatment group<br>12 weeks of monotherapy and 24 weeks of combination with Metformin | Drug: Gosogliptin<br>* 20 mg per day, dose titration to 30 mg per day at Week 4 as required Administration: orally<br>Drug: Metformin<br>* 1000 mg per day starting Week 12 (500 mg twice a day), dose titration to 2000 mg per day at Week 16 as required (1000 mg twice a day). Administration: orally<br>|
| Active Comparator: Vildagliptin treatment group<br>12 weeks of monotherapy and 24 weeks of combination with Metformin | Drug: Vildagliptin<br>* 50 mg per day, dose titration to 100 mg per day at Week 4 as required (50 mg twice a day) Administration: orally<br>Drug: Metformin<br>* 1000 mg per day starting Week 12 (500 mg twice a day), dose titration to 2000 mg per day at Week 16 as required (1000 mg twice a day). Administration: orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of HbA1c | Gosogliptin treatment group vs. Vildagliptin treatment group | at Weeks 12 and 36 from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c level of ≤7% | Percent of patients who reach the target HbA1c | at Weeks 12 and 36 from baseline | 
| Hypoglycemic episodes | Incidence of hypoglycemic episodes during the monotherapy and in combination with Metformin | up to 36 week | 
| Fasting plasma glucose | Change of fasting plasma glucose from baseline | at Weeks 12 and 36 | 
| Change of Body Mass | Change of Body Mass from baseline | at Weeks 12 and 36 | 
| Adverse event | AE rate | up to 40 week |