a study to assess the efficacy and safety of ipragliflozin in subjects with type 2 diabetes mellitus who have inadequate glycemic control on metformin

Conditions: Type 2 Diabetes Mellitus

Summary: the main purpose of this study is to evaluate the efficacy in reducing glycated hemoglobin of ipragliflozin in combination with metformin compared with metformin plus placebo in subjects with type 2 diabetes mellitus who have inadequate glycemic control on metformin.

this is a phase 3, double-blind, randomized study to assess the efficacy and safety of ipragliflozin in combination with metformin compared to metformin plus placebo in subjects in russia with type 2 diabetes mellitus who have inadequate glycemic control on metformin. subjects will enter a 10-day (± 3 days) screening period, followed by a 2-week single-blind placebo run-in period, followed by a 24-week randomized double-blind treatment period and a 4-week follow-up period

Eligibility criteria:
inclusion criteria: * subject has been diagnosed with type 2 diabetes mellitus at least 12 weeks before visit 1. * subject has been on a stable dose and a daily dose regimen of metformin ≥ 1500 mg for at least 12 weeks prior to visit 1. * subject has hba1c ≥ 7.5% and ≤ 11.0% at visit 1. * subject has been on a stable diet and exercise program for at least 12 weeks prior to visit 1 and is willing to maintain this program for the duration of the treatment period. * subject has a body mass index (bmi) of 20 to 45 kg/m2, inclusive, at visit 1. * subjects are allowed to continue taking their medication for concomitant diseases (including over-the-counter products), provided they have been on a stable dose for a minimum of 30 days prior to visit 1. * female subjects must either: 1. be of non-childbearing potential: * postmenopausal (defined as at least 1 year without any menses) prior to screening, or * documented as surgically sterile 2. or, if of childbearing potential, * agree not to try to become pregnant during the study and for 28 days after the final study drug administration * and have a negative serum pregnancy test at visit 1 * and, if heterosexually active, agree to consistently use 2 forms of highly effective birth control (at least 1 of which must be a barrier method) starting at screening, throughout the study period and for 28 days after the final study drug administration. * female subjects must agree not to breastfeed starting at screening, throughout the study period and for 28 days after the final study drug administration. * female subjects must not donate ova starting at screening, throughout the study period and for 28 days after the final study drug administration. * male subjects and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least 1 of which must be a barrier method) starting at screening and continue throughout the study period. * male subjects must not donate sperm starting at screening and throughout the study period. exclusion criteria: * subject has type 1 diabetes mellitus. * subject has received any medication for glycemic control, with the exception of metformin, (e.g., oral antidiabetic drugs, insulin, etc.) within 12 weeks prior to visit 1. * subject is currently receiving an excluded medication or has received insulin within 12 weeks prior to visit 1 or during the screening period. * subject has a history of stroke, unstable angina, myocardial infarction, any vascular intervention or heart failure (new york heart association class iii-iv;) within 12 weeks prior to visit 1. * 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. * subject has a history of diabetic coma or precoma. * subject has a history of ketoacidosis or lactic acidosis. * history of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 ml of beer \[5%\] or 35 ml of spirits \[35%\] or 100 ml of wine \[12%\]) (\> 14 units of alcohol for female subjects) or history of drugs abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates) within 3 months prior to visit 1. * subject is known to have hepatitis or be a carrier of hepatitis b surface antigen (hbsag), hepatitis c virus (hcv) antibody or is known to be positive for human immunodeficiency virus (hiv)-1 and/or hiv-2. * subject has a severe infection, has serious trauma, or is a perioperative subject. * subject has symptomatic urinary tract infection or genital infection at visit 1 and/or just prior to randomization at visit 3. * subject has uncontrolled severe hypertension (or subject whose systolic blood pressure is \> 180 mmhg or diastolic blood pressure of \> 110 mmhg measured in a sitting position after 5 minutes of rest at visit 1). * subject has an alanine aminotransferase (alt) and/or aspartate aminotransferase (ast) \> 2 x the upper limit of normal (uln) range or has a total bilirubin \> 1.5 x uln at visit 1. * subject has a urinary microalbumin/creatinine ratio ≥ 300 mg/g at visit 1. * subject has estimated glomerular filtration rate (gfr) value of \< 60 ml/min/1.73 m2 at visit 1 (using the modification of diet in renal disease \[mdrd\] calculation). * subject has known or suspected hypersensitivity to ipragliflozin or any components of the formulations used or a history of allergy for sodium-glucose cotransporter (sglt)2 inhibitors. * subject has previously received ipragliflozin or other sglt2 inhibitors. * 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 or plans to receive another investigational drug during the study. * female subject who is currently pregnant or lactating * male or female subject who does not use appropriate contraception during the study. * the subject is unable to adhere to the treatment regimen, protocol procedures or study requirements (including discontinuation criteria during the run-in period), in the investigator's judgment. * subject has an unstable medical or psychiatric illness.

Keywords: type 2 diabetes mellitus asp1941 ipragliflozin