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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: ipragliflozin; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Baja, Hungary, 6500
  • Balatonfured, Hungary, 8230
  • Budapest, Hungary, 1036
  • Budapest, Hungary, 1076
  • Gyongyos, Hungary, 3200
  • Mako, Hungary, 6900
  • Nyiregyhaza, Hungary, 4400
  • Zalaegerszeg, Hungary, 8900
• Italy
  • Ancona, Italy, 60100
  • Milan, Italy, 20132
  • Sienna, Italy, 53100
• Poland
  • Chrzanow, Poland, 32-500
  • Katowice, Poland, 40-752
  • Krakow, Poland, 30-015
  • Krakow, Poland, 30-550
  • Kutno, Poland, 99-330
  • Lodz, Poland, 90-302
  • Lublin, Poland, 20-044
  • Warszawa, Poland, 03-003
  • Wroclaw, Poland, 50-349
  • Wroclaw, Poland, 50-127
• Romania
  • Brasov, Romania, 500269
  • Brasov, Romania, 500365
  • Bucharest, Romania, 020475
  • Bucharest, Romania, 010492
  • Bucharest, Romania, 011234
  • Bucuresti, Romania, 020475
  • Bucuresti, Romania, 020275
  • Bucuresti, Romania, 20045
  • Constanta, Romania, 900675
  • Craiova, Romania, 200642
  • Lasi, Romania, 700547
  • Ploiesti, Romania, 100163
  • Ploiesti, Romania, 100018
  • Sibiu, Romania, 550245
  • Sibiu, Romania, 550371
• United Kingdom
  • Birmingham, United Kingdom, B15 2SQ
  • Cambridgeshire, United Kingdom, CB8 9PW
  • Manchester, United Kingdom, M15 6SX
  • Reading, United Kingdom, RG2 0TG
• United States
  • California
    • Los Angeles, California, United States, 90036
  • Florida
    • Coral Gables, Florida, United States, 33134
    • Hialeah, Florida, United States, 33012
    • Kissimmee, Florida, United States, 34741
  • Nevada
    • Las Vegas, Nevada, United States, 89106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP1941 lowest dose; oral tablet	Drug: ipragliflozin; oral tablet; Other Names: ASP1941; Drug: Metformin; oral tablet
Experimental: ASP1941 low dose; oral tablet	Drug: ipragliflozin; oral tablet; Other Names: ASP1941; Drug: Metformin; oral tablet
Experimental: ASP1941 high dose; oral tablet	Drug: ipragliflozin; oral tablet; Other Names: ASP1941; Drug: Metformin; oral tablet
Experimental: ASP1941 highest dose; oral tablet	Drug: ipragliflozin; oral tablet; Other Names: ASP1941; Drug: Metformin; oral tablet
Placebo Comparator: Placebo; oral tablet	Drug: Placebo; oral tablet; Drug: Metformin; oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HbA1c at Week 12	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Ude Central Contact, Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• Kashiwagi A, Shestakova MV, Ito Y, Noguchi M, Wilpshaar W, Yoshida S, Wilding JPH. Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials. Diabetes Ther. 2019 Dec;10(6):2201-2217. doi: 10.1007/s13300-019-00699-8. Epub 2019 Oct 12.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: May 4, 2010
• First Submitted That Met QC Criteria: May 4, 2010
• First Posted (Estimated): May 5, 2010

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: diabetes; Type 2 diabetes; metformin; ASP1941
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Metformin; Ipragliflozin
• Other Study ID Numbers: 1941-CL-0005; 2009-013881-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR