Phase IIb, 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 Subjects with Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone

• Conditions: Type 2 Diabetes Mellitus; MedDRA version: 12.1Level: HLGTClassification code 10018424Term: Glucose metabolism disorders (incl diabetes mellitus)

• Registration Number: EUCTR2009-013881-25-HU
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-21
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 630

Inclusion Criteria

· Subject is male or female of ³ 18 years of age at Visit 1.
· Subject has been diagnosed with 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 placebo 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. Acceptable
methods of contraception are: oral or injectable hormonal
contraceptives, contraceptive patch, intra-uterine devices, vaginal
hormonal rings, or sterilization by surgery and only in combination
with a male condom, a vaginal diaphragm or cervical caps. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 antidiabetic
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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of a 12-week treatment of 4 doses of ASP1941<br>in combination with metformin compared to placebo in combination<br>with metformin in subjects with Type 2 Diabetes Mellitus (T2DM) who<br>have inadequate glycemic control on metformin alone.;Secondary Objective: To evaluate the safety and tolerability, pharmacodynamics (PD) and<br>pharmacokinetics (PK) of 4 doses of ASP1941 in combination with<br>metformin compared to placebo in combination with metformin.;Primary end point(s): Change from baseline in HbA1c at Week 12.