Diabetic Nephropathy
Conditions
Keywords
Diabetic Nephropathy, Canagliflozin, Canaglu, Diabetes Mellitus, Type 2
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Canagliflozin (TA-7284) in Japanese patients with Diabetic Nephropathy, compared with placebo
Interventions
DRUGCanagliflozin
Canagliflozin 100mg orally once daily
DRUGPlacebo
Placebo orally once daily
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
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Additional criteria check may apply for qualification: * Glycated hemoglobin(HbA1c) of ≥6.5% and ≤12.0% * eGFR of ≥30 mL/min/1.73m2 and \<90 mL/min/1.73m2 * The median UACR of the first morning void urine samples is ≥300 mg/g Cr and ≤5000 mg/g Cr * Patients who are taking on angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) * Patients who are under dietary management and taking therapeutic exercise for diabetes
Exclusion criteria
Additional criteria check may apply for qualification: * Type I diabetes, diabetes mellitus resulting from pancreatic disorder, or secondary diabetes * A diagnosis of non-diabetic renal disease * Hereditary glucose-galactose malabsorption or primary renal glucosuria * Class IV heart failure symptoms according to New York Heart Association (NYHA) functional classification * Severe hepatic disorder or severe renal disorder * Blood potassium level \>5.5 mmoL/L * Stable blood pressure (diastolic blood pressure (DBP) ≥100mmHg or systolic blood pressure (SBP) ≥180mmHg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 30% Decline in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 104 | Week 104 | Percentage of participants with 30% decline in eGFR was calculated by multiple imputation method for missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 40% Decline in eGFR From Baseline at Week 104 | Week 104 | Percentage of participants with 40% decline in eGFR was calculated by multiple imputation method for missing data. |
| Change From Baseline in eGFR at Week 104 | Baseline and Week 104 | — |
| Composite Endpoint of End-stage Renal Disease (ESRD), Doubling of Serum Creatinine, Renal Death, and Cardiovascular (CV) Death | up to approximately 108 weeks | — |
| Change From Baseline in Percentage of Urine Albumin-to -Creatinine Ratio (UACR) at Week 104 | Baseline and Week 104 | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canagliflozin 100mg Canagliflozin 100mg orally once daily for 104 Weeks | 154 |
| Placebo Placebo orally once daily for 104 Weeks | 154 |
| Total | 308 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 10 |
| Overall Study | Physician Decision | 3 | 3 |
| Overall Study | Progressive Disease | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 13 |
Baseline characteristics
| Characteristic | Canagliflozin 100mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 10.5 | 62.4 years STANDARD_DEVIATION 11.1 | 62.5 years STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized Asian(Japanese) | 154 Participants | 154 Participants | 308 Participants |
| Sex: Female, Male Female | 39 Participants | 25 Participants | 64 Participants |
| Sex: Female, Male Male | 115 Participants | 129 Participants | 244 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 154 | 2 / 154 |
| other Total, other adverse events | 106 / 154 | 106 / 154 |
| serious Total, serious adverse events | 43 / 154 | 33 / 154 |
Outcome results
Primary
Percentage of Participants With 30% Decline in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 104
Percentage of participants with 30% decline in eGFR was calculated by multiple imputation method for missing data.
Time frame: Week 104
Population: Full Analysis Set. All Patients were analyzed according to their randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canagliflozin 100mg | Percentage of Participants With 30% Decline in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 104 | 18.2 Percentage of Participants |
| Placebo | Percentage of Participants With 30% Decline in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 104 | 29.5 Percentage of Participants |
95% CI: [1.2, 21.5]
Secondary
Change From Baseline in eGFR at Week 104
Time frame: Baseline and Week 104
Population: For Canagliflozin 100mg, Outcome measure for 30 patients was not assessed at a certain timepoint due to dropout.~For Placebo, Outcome measure for 27 patients was not assessed at a certain timepoint due to dropout.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100mg | Change From Baseline in eGFR at Week 104 | -10.39 mL/min/1.73m^2 | Standard Error 0.83 |
| Placebo | Change From Baseline in eGFR at Week 104 | -11.49 mL/min/1.73m^2 | Standard Error 0.83 |
p-value: 0.35195% CI: [-1.21, 3.4]Mixed Models Analysis
Secondary
Change From Baseline in Percentage of Urine Albumin-to -Creatinine Ratio (UACR) at Week 104
Time frame: Baseline and Week 104
Population: Canagliflozin 100mg: Outcome measure for 30 patients was not assessed at a certain timepoint due to dropout.~Placebo: Outcome measure for 27 patients was not assessed at a certain timepoint due to dropout.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Canagliflozin 100mg | Change From Baseline in Percentage of Urine Albumin-to -Creatinine Ratio (UACR) at Week 104 | 0.612 percent change |
| Placebo | Change From Baseline in Percentage of Urine Albumin-to -Creatinine Ratio (UACR) at Week 104 | 1.178 percent change |
p-value: <0.00195% CI: [0.418, 0.646]Mixed Models Analysis
Secondary
Composite Endpoint of End-stage Renal Disease (ESRD), Doubling of Serum Creatinine, Renal Death, and Cardiovascular (CV) Death
Time frame: up to approximately 108 weeks
Population: Full Analysis Set. All Patients were analyzed according to their randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canagliflozin 100mg | Composite Endpoint of End-stage Renal Disease (ESRD), Doubling of Serum Creatinine, Renal Death, and Cardiovascular (CV) Death | 24.29 Event rate per 1000 patient-years |
| Placebo | Composite Endpoint of End-stage Renal Disease (ESRD), Doubling of Serum Creatinine, Renal Death, and Cardiovascular (CV) Death | 38.66 Event rate per 1000 patient-years |
p-value: 0.29395% CI: [0.23, 1.55]Regression, Cox
Secondary
Percentage of Participants With 40% Decline in eGFR From Baseline at Week 104
Percentage of participants with 40% decline in eGFR was calculated by multiple imputation method for missing data.
Time frame: Week 104
Population: Full Analysis Set. All Patients were analyzed according to their randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canagliflozin 100mg | Percentage of Participants With 40% Decline in eGFR From Baseline at Week 104 | 10.1 percentage of Participants |
| Placebo | Percentage of Participants With 40% Decline in eGFR From Baseline at Week 104 | 13.9 percentage of Participants |
95% CI: [-4.1, 11.7]