A Study to Assess the Efficacy and Safety of ASP1941 in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of ASP1941 50mg once daily in combination with metformin and sitagliptin against placebo in combination with metformin and sitagliptin over a 24 week treatment period in subjects with type 2 diabetes mellitus with inadequate glycemic control on metformin and sitagliptin.

Official Title
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A Phase 3, Multicenter, Double-Blind, Randomized, Parallel-group, Placebo-Controlled Study to Assess the Efficacy and Safety of ASP1941 in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: ASP1941
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has been diagnosed with type 2 diabetes mellitus. Subject has an HbA1c value between 7.0% and 10.5 % at visit 1. Subject shows FPG (Fasting Plasma Glucose) value is less than 270mg/dL. Subject shows a BMI of 20.0 to 45.0 kg/m2. Subject is on stable diet and exercise program at least 8 weeks prior to study participation. Postmenopausal female or surgically sterile female or agree not to become pregnant. Exclusion Criteria: Subject has type 1 diabetes mellitus. Subject has proliferative diabetic retinopathy. Subject has a history of clinically significant renal disease(s) such as renovascular occlusive disease, nephrectomy, or renal transplant. Subject has significant dysuria caused by a neurogenic bladder or a benign prostatic hypertrophy etc. Subject has a symptomatic urinary tract infection or genital infection. Subject has chronic disease(s) that require the continuous use of systemic corticosteroids or immunosuppressants. Subject has cardiovascular disease or cerebrovascular disease that may affect the administration of ASP1941 or its safety assessment in the opinion of the investigator or sub-investigator. Subject has uncontrollable psychiatric disorder(s) with medication. Male subject is not willing to use appropriate contraception during the study. Subject has severe infection, serious trauma, or perioperative subject. Subject has a malignant tumor or has a history of malignant tumor. Subject has severe gastrointestinal disease, or history of operation for serious gastrointestinal disease. Subject has diabetic ketoacidosis. Subject has lactic acidosis or has history of lactic acidosis. Subject has hepatitis or is a carrier of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or is positive for HIV-1 and/or HIV-2. Subject has a history of thyroid dysfunction and acute pancreatitis. Subject is on weight-loss program or weight-loss medication (e.g. orlistat, phentermine/topiramate, lorcaserin) within 12 weeks of study participation. Subject has a history of serious cardiac diseases (NYHA Class III to IV), congestive heart failure, arrhythmia in need of medical treatment. Subject has a history of cerebrovascular attack, unstable angina, myocardial infarction, angioplasty, within 52 weeks (364 days) of study participation. Subject has uncontrollable severe hypertension, i.e., systolic blood pressure of higher than 180 mmHg or diastolic blood pressure of higher than 110mmHg measured in a sitting position after a 5-minute rest. Subject has following AST or ALT value: AST: Male > 100 U/L, Female > 80 U/L ALT: Male > 102.5 U/L, Female > 82.5 U/L Subject has following serum creatinine value: Creatinine: Male > 1.3 mg/dL, Female > 1.2 mg/dL Subject has estimated GFR values, of < 60 mL/min/1.73m2.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 74 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP1941 group<br>once daily over a 24 week treatment | Drug: ASP1941<br>* oral<br>* Other names: Suglat;|
| Placebo Comparator: Placebo group<br>once daily over a 24 week treatment | Drug: Placebo<br>* 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 at the end of treatment |  | at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Fasting plasma glucose at the end of treatment |  | at 24 weeks | 
| Change from baseline in Fasting serum insulin at the end of treatment |  | at 24 weeks | 
| Change from baseline in Body weight at the end of treatment |  | at 24 weeks | 
| Change from baseline in Waist circumference at the end of treatment |  | at 24 weeks | 
| Safety assessed by development of adverse events, vital signs, laboratory tests, and 12-lead ECG | ECG: Electrocardiogram | up to 24 weeks | 
| Number of subjects achieving the target HbA1c(<6.5% and <7.0%) at each visit |  | at 4, 8, 12, 16 and 24 weeks | 
| Percentage of subjects achieving the target HbA1c(<6.5% and <7.0%) at each visit |  | at 4, 8, 12, 16 and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP1941, Type 2 diabetes mellitus