An Efficacy, Safety, and Tolerability Study for TA-7284 in Patients With Type 2 Diabetes

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Dose-Ranging Study in Subjects With Type 2 Diabetes Mellitus to Evaluate the Efficacy, Safety, and Tolerability of Orally-Administered SGLT2 Inhibitor TA-7284

The purpose of this study is to demonstrate the efficacy, safety, and tolerability of TA-7284 compared with placebo in patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is well recognized as a major public health problem that presents patients with a significant risk of complications including heart disease, retinopathy, nephropathy, and neuropathy. Various classes of orally administered antihyperglycemic agents have been developed for the treatment of T2DM and although individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients, resulting in high rates of morbidity and mortality in the diabetic population. This is a randomized, double-blind, placebo-controlled, parallel-group study to demonstrate the efficacy, safety, and tolerability of TA-7284 compared with placebo in patients with T2DM, who are not optimally controlled on diet and exercise. The primary study hypothesis is that the study drug will be superior to placebo as assessed by the change in HbA1c from baseline. The patients will receive tablets of TA-7284, or placebo, once daily for 12 weeks.

Inclusion Criteria:

• Aged from 20 to 80 years inclusive on the day of informed consent;
• Patients who was diagnosed with type 2 diabetes mellitus at least 3 months before the start of the run-in period;
• Patients with HbA1c of ≥6.5% and ≤9.5% (according to the Japan Diabetic Society [JDS] criteria) on the start day of the run-in period;

Exclusion Criteria:

• Type I diabetes mellitus, diabetes mellitus resulting from pancreatic disorder, or secondary diabetes mellitus (acromegaly, Cushing's syndrome, etc.);
• Past or current history of severe diabetic complications (proliferative diabetic retinopathy, stage III or later stage overt nephropathy, diabetic ketoacidosis, or serious diabetic neuropathy);
• Fasting blood glucose of >270 mg/dL on the start day of the run-in period or at Week 2 of the run-in period;
• eGFR of <60 mL/min/1.73 m2 on the start day of the run-in period;
• Systolic blood pressure of ≥160 mmHg or diastolic blood pressure of ≥100 mmHg on the start or end day of the run-in period;
• History of myocardial infarction, unstable angina, or cerebrovascular disorder within 3 months before the start of the run-in period;
• Concurrent serious (e.g., requiring inpatient hospitalization or surgical intervention) renal or hepatic disease;
• Past or current history of malignant tumor; however, this criterion shall not apply to those who have been free of relapse for at least 5 years even with a history of malignant tumor.
• Past or current history of drug hypersensitivity such as shock and anaphylactoid symptoms;
• Pregnant women, lactating mothers, or women of childbearing potential;
• Any condition that subjects are assessed to be ineligible by the investigator (sub investigator).