Type 2 Diabetes Mellitus
Conditions
Keywords
TA-7284, JNJ-28431754, Canagliflozin, Type 2 diabetes mellitus, Sodium Glucose Co-transporter (SGLT2 inhibitor)
Brief summary
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.
Detailed description
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.
Interventions
DRUGTA-7284-Low
TA-7284-Low
DRUGTA-7284-Low-middle
TA-7284-Low-middle
DRUGTA-7284-High-middle
TA-7284-High-middle
DRUGTA-7284-High
TA-7284-High
DRUGPlacebo
Placebo
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value) | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Fasting Blood Glucose, Body Weight | 12 weeks |
| Safety and Tolerability | 14 weeks |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TA-7284-Low TA-7284 50 mg, once daily for 12 weeks | 82 |
| TA-7284-Low-middle TA-7284 100 mg, once daily for 12 weeks | 74 |
| TA-7284-High-middle TA-7284 200 mg, once daily for 12 weeks | 77 |
| TA-7284-High TA-7284 300 mg, once daily for 12 weeks | 75 |
| Placebo TA-7284 Placebo, once daily for 12 weeks | 75 |
| Total | 383 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 1 | 0 |
| Overall Study | Fasting plasma glucose level increased | 1 | 0 | 0 | 0 | 7 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | TA-7284-Low | TA-7284-Low-middle | TA-7284-High-middle | TA-7284-High | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 57.4 years STANDARD_DEVIATION 10.8 | 57.7 years STANDARD_DEVIATION 10.5 | 57 years STANDARD_DEVIATION 10.6 | 57.1 years STANDARD_DEVIATION 10.1 | 57.7 years STANDARD_DEVIATION 11 | 57.4 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 32 Participants | 22 Participants | 27 Participants | 20 Participants | 21 Participants | 122 Participants |
| Sex: Female, Male Male | 50 Participants | 52 Participants | 50 Participants | 55 Participants | 54 Participants | 261 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 82 | 34 / 74 | 38 / 77 | 34 / 75 | 26 / 75 |
| serious Total, serious adverse events | 1 / 82 | 0 / 74 | 0 / 77 | 0 / 75 | 0 / 75 |
Outcome results
Primary
Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value)
Time frame: 12 weeks
Population: Full analysis set, last observation carried forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TA-7284-Low | Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value) | -0.61 percent HbA1C | Standard Error 0.06 |
| TA-7284-Low-middle | Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value) | -0.80 percent HbA1C | Standard Error 0.06 |
| TA-7284-High-middle | Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value) | -0.79 percent HbA1C | Standard Error 0.06 |
| TA-7284-High | Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value) | -0.88 percent HbA1C | Standard Error 0.06 |
| Placebo | Change in Hemoglobin A1c (A1C) From Baseline (NGSP Value) | 0.11 percent HbA1C | Standard Error 0.06 |
Secondary
Fasting Blood Glucose, Body Weight
Time frame: 12 weeks
Secondary
Safety and Tolerability
Time frame: 14 weeks