Type 2 Diabetes Mellitus
Conditions
Keywords
insulin resistance
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Canagliflozin (TA-7284) in combination with Insulin in patients with type 2 Diabetes for 16 weeks administration.
Detailed description
This is a randomized, 2-arm, parallel group, double blind study to evaluate the efficacy and safety of Canagliflozin (TA-7284) in Japanese patients with type 2 diabetes mellitus, who are receiving treatment with insulin therapy on diet and exercise and have inadequate glycemic control. The patients will receive either TA-7284 100mg or Placebo orally for 16 weeks.
Interventions
The patients will receive Canagliflozin orally for 16 weeks
DRUGPlacebo
The patients will receive Placebo orally for 16 weeks
DRUGInsulin
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who has been receiving a stable dose and regimen of insulin over 12 weeks before administration of investigational dug * Patients who are under dietary management and taking therapeutic exercise for diabetes over 12 weeks before administration of investigational drug * Patients with HbA1c of ≥7.5% and \<10.5% * Patients who were not administered diabetes therapeutic drugs prohibited for concomitant use within 12 weeks before administration of investigational drug
Exclusion criteria
* Patients with type 1 diabetes mellitus, diabetes mellitus resulting from pancreatic disorder, or secondary diabetes mellitus (Cushing's syndrome, acromegaly, etc.) * Patients with severe diabetic complications (proliferative diabetic retinopathy, stage 4 nephropathy, or serious diabetic neuropathy) * Patients with hereditary glucose-galactose malabsorption or primary renal glucosuria * Patients with systolic blood pressure of ≥160 mmHg or diastolic blood pressure of ≥100 mmHg * Patients with serious renal or hepatic disease * Patients with eGFR of \<45 mL/min/1.73 m2 * Patients who are the excessive alcohol addicts * Patients who are pregnant, lactating and probably pregnant patients and patients who can not agree to contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in HbA1c From Baseline | baseline and Week 16 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Fasting Plasma Glucose | baseline and Week 16 |
| Percent Change in Body Weight | baseline and Week 16 |
| Change in Blood Pressure | baseline and Week 16 |
| Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased | Week 16 |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canagliflozin (TA-7284) ＋Insulin Canagliflozin, once daily for 16 weeks | 76 |
| Placebo＋Insulin Placebo, once daily for 16 weeks | 70 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Conflict with the stopping criteria | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Canagliflozin (TA-7284) ＋Insulin | Placebo＋Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 22 Participants | 51 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 48 Participants | 95 Participants |
| Sex: Female, Male Female | 32 Participants | 21 Participants | 53 Participants |
| Sex: Female, Male Male | 44 Participants | 49 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 39 / 75 | 34 / 71 |
| serious Total, serious adverse events | 3 / 75 | 1 / 71 |
Outcome results
Primary
Change in HbA1c From Baseline
Time frame: baseline and Week 16
Population: Full analysis set, last observation carried forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin (TA-7284) ＋Insulin | Change in HbA1c From Baseline | -0.97 Percent | Standard Error 0.08 |
| Placebo＋Insulin | Change in HbA1c From Baseline | 0.13 Percent | Standard Error 0.08 |
p-value: <0.00195% CI: [-1.33, -0.87]ANCOVA
Secondary
Change in Blood Pressure
Time frame: baseline and Week 16
Population: Full analysis set, last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canagliflozin (TA-7284) ＋Insulin | Change in Blood Pressure | Systolic blood pressure | -3.58 mmHg | Standard Error 1.14 |
| Canagliflozin (TA-7284) ＋Insulin | Change in Blood Pressure | Diastolic blood pressure | -1.55 mmHg | Standard Error 0.71 |
| Placebo＋Insulin | Change in Blood Pressure | Systolic blood pressure | -0.40 mmHg | Standard Error 1.19 |
| Placebo＋Insulin | Change in Blood Pressure | Diastolic blood pressure | -0.31 mmHg | Standard Error 0.74 |
p-value: 0.05895% CI: [-6.49, 0.11]ANCOVA
p-value: 0.23295% CI: [-3.27, 0.8]ANCOVA
Secondary
Change in Fasting Plasma Glucose
Time frame: baseline and Week 16
Population: Full analysis set, last observation carried forward. There was a lack of measurement of fasting plasma glucose at the end of treatment visit(Week 4) in one participant who was randomized to Canagliflozin(TA-7284) + Insulin group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin (TA-7284) ＋Insulin | Change in Fasting Plasma Glucose | -34.1 mg/dL | Standard Error 4.8 |
| Placebo＋Insulin | Change in Fasting Plasma Glucose | -1.4 mg/dL | Standard Error 5 |
p-value: <0.00195% CI: [-46.3, -18.9]ANCOVA
Secondary
Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased
Time frame: Week 16
Population: Safety analysis set. Safety Population reflects the as treated population, and one Canagliflozin (TA-7284) + Insulin participant actually received Placebo + Insulin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canagliflozin (TA-7284) ＋Insulin | Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased | adverse events | 68.0 percentage of participants |
| Canagliflozin (TA-7284) ＋Insulin | Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased | Hypoglycemia and Blood glucose decreased | 40.0 percentage of participants |
| Placebo＋Insulin | Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased | adverse events | 64.8 percentage of participants |
| Placebo＋Insulin | Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased | Hypoglycemia and Blood glucose decreased | 29.6 percentage of participants |
Secondary
Percent Change in Body Weight
Time frame: baseline and Week 16
Population: Full analysis set, last observation carried forward. There was a lack of measurement of body weight at the end of treatment visit(Week 4) in one participant who was randomized to Canagliflozin(TA-7284) + Insulin group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin (TA-7284) ＋Insulin | Percent Change in Body Weight | -2.13 percent change | Standard Error 0.25 |
| Placebo＋Insulin | Percent Change in Body Weight | 0.24 percent change | Standard Error 0.26 |
p-value: <0.00195% CI: [-3.09, -1.65]ANCOVA