A Study of ASP1941 in Combination With Insulin in Patients With Type 1 Diabetes Mellitus

Phase III Study of ASP1941 Double-blind, Parallel-group Study in Combination With Insulin in Patients With Type 1 Diabetes Mellitus

The objective of this study is to confirm efficacy of ASP1941 based on the changes in HbA1c and to assess its safety in subjects with type 1 diabetes mellitus receiving ASP1941 once daily in combination with insulin for 24 weeks. This study will also assess the safety/efficacy of long-term treatment (52 weeks).

This study consists of two parts. In Part 1, ASP1941 or placebo will be administered orally in a blind manner. In Part 2, the long-term safety and efficacy of ASP1941 will be evaluated in patients who have participated in the study and completed the Part 1.

Inclusion Criteria:

• The subject has been diagnosed with type 1 diabetes mellitus
• The subject has been receiving insulin therapy for the treatment of diabetes mellitus.
• The subject has not switched from an insulin product to another insulin product or switched between continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI).
• The subject has an HbA1c value between 7.5% and 11.0% and the difference of HbA1c value is within ± 2.0%.
• The subject has a fasting blood C-peptide level < 0.6 ng/mL.
• The subject has a body mass index (BMI) between 20.0 kg/m2 and 35.0 kg/m2.

Exclusion Criteria:

• The subject has type 2 diabetes mellitus.
• The subject has participated in a clinical study or post marketing study of another drug or medical equipment within 12 weeks (84 days) before providing written informed consent, or is currently participating in such a study.
• The subject has received treatment with ASP1941 (ipragliflozin) or participated in a clinical study of ASP1941 (excluding subjects who discontinued before the investigational period).
• The subject participated in this study previously.
• The subject has received a hypoglycemic agent other than insulin or an α-glucosidase inhibitor.
• The subject has proliferative retinopathy (except for those who have undergone photocoagulation etc. and whose symptoms are stable).
• The subject has experienced severe hypoglycemia.
• The subject has experienced diabetic ketoacidosis.
• The subject has chronic disease that requires the continuous use of corticosteroids, immunosuppressants, etc.
• The subject has symptomatic urinary tract infection or symptomatic genital infection.
• The subject has a history of recurrent urinary tract infection or recurrent genital infection.
• The subject has a history of cerebral vascular attack, unstable angina, myocardial infarction, vascular intervention, or another serious heart disease.
• The subject has a concomitant malignant tumor or a history of malignant tumor
• The subject has a history of an allergy to ASP1941 (ipragliflozin) and/or similar drugs (drugs possessing SGLT2 inhibitory action).
• The subject has psychiatric disorder that is inappropriate for participation in the study.
• The subject has drug addiction or alcohol abuse.
• The subject has severe infection or serious trauma, or is perioperative.
• The subject has a history of medically significant renal disease such as renovascular occlusive disease, nephrectomy and/or renal transplant.
• The subject has any symptoms of dysuria, anuria, oliguria, or urinary retention.
• The subject has severe renal impairment or end-stage renal failure requiring dialysis.
• The subject has an Aspartate Aminotransferase and/or Alanine Aminotransferase value that exceeds 2 times, or a total bilirubin value that exceeds 1.5 times the upper limit of the reference range.
• The subject has uncontrolled severe hypertension.
• The subject has serious gastrointestinal disease or a history of operation for serious gastrointestinal disease.