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

Astellas

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Metformin; Drug: ipragliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01117584

1941-CL-0005

2009-013881-25 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 343 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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343 participants in 5 patient groups, including a placebo group

ASP1941 lowest dose

Experimental group

Description:

oral tablet

Treatment:

Drug: ipragliflozin

Drug: Metformin

ASP1941 low dose

Experimental group

Description:

oral tablet

Treatment:

Drug: ipragliflozin

Drug: Metformin

ASP1941 high dose

Experimental group

Description:

oral tablet

Treatment:

Drug: ipragliflozin

Drug: Metformin

ASP1941 highest dose

Experimental group

Description:

oral tablet

Treatment:

Drug: ipragliflozin

Drug: Metformin

Placebo

Placebo Comparator group

Description:

oral tablet

Treatment:

Drug: Metformin

Drug: Placebo