Foxiga Korea Local Phase 4 Study

Study Overview
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Brief Summary
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To evaluate the effect of dapagliflozin on body composition in Korean T2DM subjects.12-month, randomised, open-label, parallel-group, multi-centre phase IV study.

Detailed Description
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This is a 52 weeks, randomized, open-label, parallel-group, multi-centres phase IV study. Participants will be randomized 1:1 to receive dapagliflozin 10 mg qd or glimepiride 1 2 mgqd in an open-label manner for 12 months as add-on to metformin 1000 mg. Parallel group study design was chosen. In order maintain the practicality of the phase IV study, open label design of study drug delivery was chosen. The reading of the DXA scans will be conducted by one expert in blinded manner. Glimepiride is the most frequently used SUs in Korea and therefore this was chosen as comparator.Dapagliflozin treatment will be associated with reduction of total body FM, BW, abdominal VAT and SAT volume compared with glimepiride.

Official Title
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Effects of Dapagliflozin Compared With Glimepiride on Body Composition in Patients With Type 2 Diabetes Inadequately Controlled With Metformin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with T2DM (Male or female, ≥ 19 and ≤ 75 yrs) Patients in insufficient glycemic control (HbA1c > 7.5% and < 9.5% in recent 4 weeks) Patients with an unchanged dose of metformin (≥ 1,000 mg/day) for > 8 weeks prior to randomization Written informed consent WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose. WOCBP must have a negative urine pregnancy test at screening visit WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. WOCBP must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator. Exclusion Criteria: Type 1 diabetes or history of diabetic ketoacidosis Pregnant or breast-feeding patients eGFR < 60 mL/min/1.73 m2 (MDRD) on visit 1. Indication of active liver disease (AST/ALT/total bilirubin > 3 X upper limits of normal) on visit 1. Acute coronary syndrome, stroke or TIA within 3 months prior to randomization Bariatric surgery within 2 years; treatment of anti-obesity drugs 3 months prior to randomization; any treatment leading to unstable body weight. (Unstable body weight is considered reliable in the judgment of the Investigator.) History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time History of any other malignancy within 5 years (with the exception of successfully treated non-melanoma skin cancers) History of alcohol or drug abuse judged by physician within 3 months prior to randomization Concomitant participation in any other clinical study.

Ages Eligible for Study
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Minimum Age: 19 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: Dapagliflozin<br>Dapagliflozin 10mg + Metformin 1000mg | Drug: Dapagliflozin<br>* Subject who will be randomized to the 'Dapagliflozin arm' will be treated with dapagliflozin 10mg + Metformin 1000 mg as Diabetes Treatment<br>|
| Active Comparator: Glimepiride<br>Glimepiriide 1-2mg + Metformin 1000mg | Drug: Glimepiride<br>* Subject who will be randomized to the 'Glimepiride arm' will be treated with glimepiride 1-2mg + Metformin 1000 mg as Diabetes Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Changes From Baseline in Total Body Fat Mass by DXA Scan | Adjusted mean changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment | From baseline to Week 52 | 
| Adjusted Mean Changes From Baseline in Percentage of Total Body Fat Assessed by DXA Scan | Adjusted mean percent changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment | From baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in HbA1c at Week 52 | Adjusted Mean Change in HbA1c at Week 52 | From baseline to Week 52 | 
| HbA1c <7.0% at Week 52 | HbA1c <7.0% at Week 52 | 52 weeks | 
| Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52 | Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Total Body Weight at Week 52 | Adjusted Mean Change in Total Body Weight at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Waist Circumference at Week 52 | Adjusted Mean Change in Waist Circumference at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Body Mass Index (BMI) at Week 52 | Adjusted Mean Change in Body Mass Index (BMI) at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52 | Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52 | Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Visceral Adipose Tissue (VAT) Area at Week 52 | Adjusted Mean Change in Visceral Adipose Tissue (VAT) area at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) Area at Week 52 | Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) area at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52 | Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Lean Body Mass at Week 52 | Adjusted Mean Change in Lean Body Mass at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in Adinopectin at Week 52 | Adjusted Mean Change in Adinopectin at Week 52 | From baseline to Week 52 | 
| Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52 | Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52 | From baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DM