E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10018424 |
E.1.2 | Term | Glucose metabolism disorders (incl diabetes mellitus) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of a 12-week treatment of 4 doses of ASP1941 in combination with metformin compared to placebo in combination with metformin in subjects with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic control on metformin alone. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of 4 doses of ASP1941 in combination with metformin compared to placebo in combination with metformin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c at Week 12. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |