Safety, Pharmacokinetics and Pharmacodynamics of TA-7284 in Type 2 Diabetic Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, pharmacokinetics and pharmacodynamics of TA-7284 orally administered once daily for 15 days (1 day followed by a 1 day washout period and then 14 consecutive days). Dose escalation design is utilized in this study, and dose escalation of TA-7284 will be starting with 25 mg (step 1). Subsequent doses of 100 mg (step 2), 200 mg (step 3) and 400 mg (step 4) are planned after review of the tolerance and PK of the previous step.

Official Title
-----------------
A Clinical Pharmacology Study of Multiple Doses of TA-7284 in Patients With Type 2 Diabetes Mellitus

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: TA-7284
* Drug: Placebo of TA-7284


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically stable Type 2 Diabetes Mellitus Females without childbearing potential Body mass index (BMI) >= 18.5 kg/m2 and <= 39.9 kg/m2 Hemoglobin A1c levels >= 6.5% and <= 10% Fasting blood glucose levels >= 140 mg/dL and <= 270 mg/dL Systolic blood pressure >= 95 mmHg and <= 160 mmHg, and diastolic blood pressure >= 50 mmHg and <= 100 mmHg, and pulse rate >= 50 bpm Patients who have not been administered anti-diabetic medication within 2 weeks Prior to dosing Medicines if necessary for Hypertension or Dyslipidemia should be administered with stable dosage at least 3 months Treatment with diet and exercise should be unchanged for more than 3 months Exclusion Criteria: Type 1 Diabetes Mellitus or Secondary Diabetic Mellitus History of diabetic complications which need treatment Treatment with insulin, thiazolidinediones, thiazide diuretics、beta blockers or systemic steroids within 3 months prior to informed consent Serum creatinine > upper limit of the normal range Patients with significant complications

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TA-7284<br> | Drug: TA-7284<br>* Patients will receive single ascending dose of TA-7284 in each step (4 doses planned: 25, 100, 200 and 400 mg), once daily, 15 days (1 day followed by a 1 day washout period and then 14 consecutive days)<br>|
| Placebo Comparator: Placebo of TA-7284<br> | Drug: Placebo of TA-7284<br>* Patients will receive placebo tablets in each step, once daily, 15 days (1 day followed by a 1 day washout period and then 14 consecutive days)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Adverse Events, Adverse Drug Reactions | In the safety analysis population, adverse events incidences and adverse drug reactions incidences were calculated by dose. | 19 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics- 1)Plasma Concentration of TA-7284: Tmax,Cmax, AUC, Etc.; and 2)Urinary Excretion of TA-7284: Ae, Ae%, CLr |  | 19 days | 
| Pharmacodynamics- 1)Urinary Glucose Excretion; 2)Plasma Glucose Concentration; 3)Insulin Concentration in Serum; 4)Insulinogenic Index;and 5)Hemoglobin A1c and Glycoalbumin |  | 18 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, TA-7284