Type 2 Diabetes Mellitus
Conditions
Keywords
TA-7284, JNJ-28431754, Canagliflozin, Renal Impairment, Sodium Glucose Co-transporter2 (SGLT2) inhibitor
Brief summary
The purpose of this study is to evaluate the PK/PD and safety of TA-7284 in patients with type 2 diabetes mellitus who have moderate renal impairment.
Detailed description
This is an open-label, randomized, 2-way crossover study to evaluate the PK/PD and safety of TA-7284 in patients with type 2 diabetes mellitus who have moderate renal impairment relative to patients with type 2 diabetes mellitus who have normal renal function. The patients will receive both TA-7284-Low and TA-7284-High orally alone in either Period 1 or 2.
Interventions
DRUGTA-7284 Low
Low
DRUGTA-7284 High
High
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus in stable condition who have normal renal function or moderate renal impairment * Body mass index of ≥18.5 kg/m2 and ≤39.9 kg/m2 at screening * HbA1c of ≥6.5% and ≤10.5% at screening
Exclusion criteria
* Type 1 diabetes mellitus, diabetes mellitus resulting from pancreatic disorder, secondary diabetes mellitus * Past or current history of severe diabetic complications * Patients requiring insulin therapy * History of hereditary glucose-galactose malabsorption or primary renal glucosuria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Renal Function on Percent Inhibition of Renal Glucose Reabsorption (RGR) of TA-7284 | For 24 hours after each administration | The percent inhibition of renal glucose reabsorption was calculated from renal glucose reabsorption (eGFR × plasma glucose AUC - urinary glucose excretion) on the preceding day and on the day of administration. |
| Effect of Renal Function on Maximum Plasma Concentration of TA-7284 | For 72 hours after each administration | — |
| Effect of Renal Function on Area Under the Plasma Concentration-time Curve From Zero up to Infinity of TA-7284 | For 72 hours after each administration | — |
| Effect of Renal Function on Urinary Glucose Excretion of TA-7284 | For 24 hours after each administration | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Upto approximately 14 days after last administration | Incidence and severity of AEs |
| 12-lead Electrocardiogram (ECG) | For 72 hours after each administration | Change from baseline in ECG parameters |
| Vital Signs | For 72 hours after each administration | Change from baseline in Vital signs (BP, PR and BT) |
| Clinical Laboratory Tests | For 72 hours after each administration | Change from baseline in Clinical laboratory tests |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Population for Moderate Renal Impairment | 12 |
| Entire Population for Normal Renal Function | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Entire Population for Moderate Renal Impairment | Entire Population for Normal Renal Function | Total |
|---|---|---|---|
| Age, Continuous | 63.7 years FULL_RANGE 10.2 | 57.8 years FULL_RANGE 9.7 | 60.8 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 12 | 1 / 12 | 2 / 12 | 3 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Effect of Renal Function on Area Under the Plasma Concentration-time Curve From Zero up to Infinity of TA-7284
Time frame: For 72 hours after each administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Renal Impairment Low | Effect of Renal Function on Area Under the Plasma Concentration-time Curve From Zero up to Infinity of TA-7284 | 8766 ng･h/mL | Standard Deviation 2551 |
| Moderate Renal Impairment High | Effect of Renal Function on Area Under the Plasma Concentration-time Curve From Zero up to Infinity of TA-7284 | 17835 ng･h/mL | Standard Deviation 4434 |
| Normal Renal Function Low | Effect of Renal Function on Area Under the Plasma Concentration-time Curve From Zero up to Infinity of TA-7284 | 6929 ng･h/mL | Standard Deviation 1734 |
| Normal Renal Function High | Effect of Renal Function on Area Under the Plasma Concentration-time Curve From Zero up to Infinity of TA-7284 | 14815 ng･h/mL | Standard Deviation 4162 |
Primary
Effect of Renal Function on Maximum Plasma Concentration of TA-7284
Time frame: For 72 hours after each administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Renal Impairment Low | Effect of Renal Function on Maximum Plasma Concentration of TA-7284 | 1197.1264 ng / mL | Standard Deviation 310.5625 |
| Moderate Renal Impairment High | Effect of Renal Function on Maximum Plasma Concentration of TA-7284 | 2333.3617 ng / mL | Standard Deviation 414.8957 |
| Normal Renal Function Low | Effect of Renal Function on Maximum Plasma Concentration of TA-7284 | 1213.6571 ng / mL | Standard Deviation 337.8705 |
| Normal Renal Function High | Effect of Renal Function on Maximum Plasma Concentration of TA-7284 | 2415.6109 ng / mL | Standard Deviation 739.8783 |
Primary
Effect of Renal Function on Percent Inhibition of Renal Glucose Reabsorption (RGR) of TA-7284
The percent inhibition of renal glucose reabsorption was calculated from renal glucose reabsorption (eGFR × plasma glucose AUC - urinary glucose excretion) on the preceding day and on the day of administration.
Time frame: For 24 hours after each administration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Moderate Renal Impairment Low | Effect of Renal Function on Percent Inhibition of Renal Glucose Reabsorption (RGR) of TA-7284 | 60.8 percent of RGR at baseline |
| Moderate Renal Impairment High | Effect of Renal Function on Percent Inhibition of Renal Glucose Reabsorption (RGR) of TA-7284 | 66.5 percent of RGR at baseline |
| Normal Renal Function Low | Effect of Renal Function on Percent Inhibition of Renal Glucose Reabsorption (RGR) of TA-7284 | 47.8 percent of RGR at baseline |
| Normal Renal Function High | Effect of Renal Function on Percent Inhibition of Renal Glucose Reabsorption (RGR) of TA-7284 | 52.7 percent of RGR at baseline |
Primary
Effect of Renal Function on Urinary Glucose Excretion of TA-7284
Time frame: For 24 hours after each administration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Moderate Renal Impairment Low | Effect of Renal Function on Urinary Glucose Excretion of TA-7284 | 61.017 g |
| Moderate Renal Impairment High | Effect of Renal Function on Urinary Glucose Excretion of TA-7284 | 70.904 g |
| Normal Renal Function Low | Effect of Renal Function on Urinary Glucose Excretion of TA-7284 | 86.592 g |
| Normal Renal Function High | Effect of Renal Function on Urinary Glucose Excretion of TA-7284 | 103.052 g |
Secondary
12-lead Electrocardiogram (ECG)
Change from baseline in ECG parameters
Time frame: For 72 hours after each administration
Secondary
Adverse Events
Incidence and severity of AEs
Time frame: Upto approximately 14 days after last administration
Secondary
Clinical Laboratory Tests
Change from baseline in Clinical laboratory tests
Time frame: For 72 hours after each administration
Secondary
Vital Signs
Change from baseline in Vital signs (BP, PR and BT)
Time frame: For 72 hours after each administration