Clinical trial NCT02794792 (phase 3, status: completed)
Conditions: type 2 diabetes mellitus
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: ipragliflozin l-proline, metformin, placebo
SMILES: OC[C@H]1O[C@H]([C@H](O)[C@@H](O)[C@@H]1O)C1=CC=C(F)C(CC2=CC3=CC=CC=C3S2)=C1, CSCC[C@H](N)C(O)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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.