Clinical trial NCT01117584: A Study to Evaluate the Effect of ASP1941 in Combination With Metformin in Adult Patients With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes
ASP1941
diabetes
metformin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2010-05-05
Enrollment: 343
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in HbA1c at Week 12
timeFrame: Baseline, 12 weeks
Secondary outcomes:
measure: Change from baseline in fasting plasma glucose (FPG) at Week 12
timeFrame: Baseline, 12 weeks
measure: Achievement of target goal (HbA1c <7.0%) at Week 12
timeFrame: 12 weeks
measure: Achievement of target goal (HbA1c <6.5%) at Week 12
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Coral Gables
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Las Vegas
country: United States
state: Nevada
city: Baja
country: Hungary
city: Balatonfured
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Gyongyos
country: Hungary
city: Mako
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Ancona
country: Italy
city: Milan
country: Italy
city: Sienna
country: Italy
city: Chrzanow
country: Poland
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Krakow
country: Poland
city: Kutno
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Wroclaw
country: Poland
city: Brasov
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Bucuresti
country: Romania
city: Bucuresti
country: Romania
city: Constanta
country: Romania
city: Craiova
country: Romania
city: Lasi
country: Romania
city: Ploiesti
country: Romania
city: Ploiesti
country: Romania
city: Sibiu
country: Romania
city: Sibiu
country: Romania
city: Birmingham
country: United Kingdom
city: Cambridgeshire
country: United Kingdom
city: Manchester
country: United Kingdom
city: Reading
country: United Kingdom
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Ude Central Contact
role: STUDY_DIRECTOR
References:
citation: 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.