A Study to Evaluate the Effect of ASP1941 in Combination With Metformin in Adult Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Evaluate the efficacy, safety and tolerability of a 12-week treatment of 4 doses of ASP1941 compared to placebo in combination with metformin in adult patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin alone.

Official Title
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Phase 2b, Double-Blind, Randomized, Multicenter, Parallel Group, Placebo-Controlled, Dose-Finding Study to Evaluate the Efficacy, Safety and Tolerability of a 12-Week Treatment With ASP1941 in Combination With Metformin in Patients With Type 2Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: ipragliflozin
* Drug: Placebo
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has been diagnosed with Diabetes Mellitus type 2 (T2DM) for at least 6 months Subject has inadequate glycemic control indicated by an HbA1c level between 7.0% and 9.5% at start of the run-in period at Visit 1 AND does not meet any of the FPG discontinuation criteria Subject has been on a stable dose of at least 1500 mg/day metformin monotherapy for at least 6 weeks prior to Visit 1 Subject is on a stable diet and exercise program (for at least 6 weeks prior to Visit 1) and is willing to remain on this program for the duration of the study Subject has a body mass index (BMI) 20 - 45 kg/m2 at Visit 1 Female subject of childbearing potential has a negative serum pregnancy test (human chorionic gonadotropin [hCG]) at Visit 1 and agrees to use an acceptable form of contraception throughout the duration of the study OR is at least 1 year post-menopausal (defined as amenorrhea for at least 1 year) or surgically sterile. Male study subjects should be advised to use a male condom in addition to having their partner use another acceptable method during the study and for 3 months after the last dose Exclusion Criteria: Subject has any known complication of T2DM indicating a late disease state that in the investigator's opinion should preclude the subject from participation Subject has type 1 diabetes mellitus Subject is in need of insulin therapy or has received insulin within 3 months prior to Visit 1, with the exception of acute use of <7 days Subject has a serum creatinine higher than upper limit of normal range at Visit 1 Subject has an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 3 times upper limit of normal range or has a total bilirubin more than 2 times upper limit of normal at Visit 1 Subject has a urinary microalbumin/creatinine ratio above or equal to 300 mg/g at Visit 1 Subject has a symptomatic urinary tract infection (UTI) or symptomatic genital infection at Visit 1 or during the placebo run-in period, including just prior to randomization at Visit 2 Subject has persistent, uncontrolled severe hypertension as indicated by a systolic blood pressure >180 mmHg or a diastolic blood pressure of >110 mmHg taken in a sitting position after 5 minutes of rest on at least 2 measurements (within 30 minutes of each other) at Visit 1 Subject has a significant cardiovascular disease, such as myocardial infarction or a vascular intervention (e.g. angioplasty or stent) within 3 months prior to Visit 1, or history of heart failure (New York Heart Association [NYHA] Class III IV) Subject is known to have hepatitis or be a carrier of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (enzyme linked immunosorbent assay [ELISA] plus confirmatory test), or is known positive for human immunodeficiency virus (HIV) HIV-1 and/or HIV 2 Subject is currently receiving an excluded medication (loop-diuretics or systemic corticosteroids) or has received any other oral anti-diabetic drug except for metformin within 3 months prior to Visit 1 Subject has history of lactic acidosis Subject has a history of drug or alcohol abuse/dependency within 12 months prior to Visit 1 as defined in the Diagnostic and Statistical Manual-IV (DSM-IV) Subject has had a malignancy in the last 5 years, except for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix Female subject who is pregnant, lactating or pre-menopausal with positive serum pregnancy test (hCG) at Visit 1 or has an intention of becoming pregnant Subject has an unstable medical or psychiatric illness Subject has known or suspected hypersensitivity to ASP1941 or any components of the formulations used Subject has previously received ASP1941 Subject is concurrently participating in another drug study or has received an investigational drug within 30 days (or the limit set by national law, whichever is longer) prior to Visit 1 Subject has any concurrent illness which, in the opinion of the investigator, may interfere with treatment or evaluation of safety or completion of this study In the investigator's judgment, the subject is unable to adhere to the treatment regimen, protocol procedures or study requirements

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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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 lowest dose<br>oral tablet | Drug: ipragliflozin<br>* oral tablet<br>* Other names: ASP1941;Drug: Metformin<br>* oral tablet<br>|
| Experimental: ASP1941 low dose<br>oral tablet | Drug: ipragliflozin<br>* oral tablet<br>* Other names: ASP1941;Drug: Metformin<br>* oral tablet<br>|
| Experimental: ASP1941 high dose<br>oral tablet | Drug: ipragliflozin<br>* oral tablet<br>* Other names: ASP1941;Drug: Metformin<br>* oral tablet<br>|
| Experimental: ASP1941 highest dose<br>oral tablet | Drug: ipragliflozin<br>* oral tablet<br>* Other names: ASP1941;Drug: Metformin<br>* oral tablet<br>|
| Placebo Comparator: Placebo<br>oral tablet | Drug: Placebo<br>* oral tablet<br>Drug: Metformin<br>* oral tablet<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 Week 12 |  | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting plasma glucose (FPG) at Week 12 |  | Baseline, 12 weeks | 
| Achievement of target goal (HbA1c <7.0%) at Week 12 |  | 12 weeks | 
| Achievement of target goal (HbA1c <6.5%) at Week 12 |  | 12 weeks | 

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