Diabetes Mellitus, Type 2
Conditions
Brief summary
To evaluate the efficacy of empagliflozin administered orally once daily in postprandial glucose and 24-hour glycaemic variability compared to placebo given for 4 weeks as mono-therapy in Japanese patients with type 2 diabetes mellitus with insufficient glycaemic control on no antidiabetic treatment.
Interventions
DRUGPlacebo
Placebo tablet matching Empagliflozin low dose
DRUGEmpagliflozin
Empagliflozin low dose
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of type 2 diabetes mellitus prior to informed consent * Male and female patients on diet and exercise regimen for 12 weeks prior to informed consent who are: * drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent or, * pre-treated with one oral antidiabetic drug (except sulfonylurea and thiazolidinedione); the present antidiabetic therapy has to be unchanged for at least 12 weeks prior to the informed consent. (Sulfonylurea is permitted as pre-treatment drug only if the dose is equal or less than a half of daily maximum approval dose.) * Glycosylated haemoglobin (HbA1c) at Visit 1 (screening) * for patients without antidiabetic therapy : HbA1c \>=7.0 to =\<10.0% * for patients with one oral antidiabetic drug : HbA1c \>=7.0 to =\<9.5%
Exclusion criteria
* Uncontrolled hyperglycaemia with a glucose level \>240 mg/dL (\>13.3 mmol/L) * Impaired renal function, defined as estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2 (moderate and severe renal impairment, modification of diet in renal disease (MDRD) formula) * Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 12 weeks prior to informed consent * Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Area Under the Concentration-time Curve (AUC1-4h) for Postprandial Plasma Glucose From Baseline After 28 Days of Treatment | 1h, 1.5h, 2h, 2.5, 3h, 3.5h and 4h after drug administration at day -1 (baseline), and 1h, 1.5h, 2h, 2.5, 3h, 3.5h and 4h after drug administration at day 28 | The primary endpoint is the change in AUC1-4h for postprandial plasma glucose based on meal tolerance test from baseline after 28 days of treatment. Baseline refers to the last observation prior to administration of randomised study medication. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablets matching empagliflozin 10 mg or 25 mg tablets | 21 |
| Empagliflozin 10 mg Empagliflozin 10 mg oral administration once daily | 20 |
| Empagliflozin 25 mg Empagliflozin 25mg oral administration once daily | 19 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Empagliflozin 10 mg | Empagliflozin 25 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 10.8 | 64.8 years STANDARD_DEVIATION 5.9 | 62.6 years STANDARD_DEVIATION 7.8 | 62.7 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 16 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 21 | 2 / 20 | 3 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 19 |
Outcome results
Primary
Change in Area Under the Concentration-time Curve (AUC1-4h) for Postprandial Plasma Glucose From Baseline After 28 Days of Treatment
The primary endpoint is the change in AUC1-4h for postprandial plasma glucose based on meal tolerance test from baseline after 28 days of treatment. Baseline refers to the last observation prior to administration of randomised study medication.
Time frame: 1h, 1.5h, 2h, 2.5, 3h, 3.5h and 4h after drug administration at day -1 (baseline), and 1h, 1.5h, 2h, 2.5, 3h, 3.5h and 4h after drug administration at day 28
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Area Under the Concentration-time Curve (AUC1-4h) for Postprandial Plasma Glucose From Baseline After 28 Days of Treatment | -18.07 mg*h/dL | Standard Error 13.89 |
| Empagliflozin 10 mg | Change in Area Under the Concentration-time Curve (AUC1-4h) for Postprandial Plasma Glucose From Baseline After 28 Days of Treatment | -103.56 mg*h/dL | Standard Error 14.24 |
| Empagliflozin 25 mg | Change in Area Under the Concentration-time Curve (AUC1-4h) for Postprandial Plasma Glucose From Baseline After 28 Days of Treatment | -122.94 mg*h/dL | Standard Error 14.35 |
Comparison: Difference calculated as empa 25 mg minus placebo. The analyses will be performed sequentially compared with placebo from high dose of empagliflozin and the full significance level (5%) will be maintained by the hierarchical procedure.p-value: <0.000195% CI: [-144.77, -64.97]ANCOVA
Comparison: Difference calculated as empa 10 mg minus placebo. The analyses will be performed sequentially compared with placebo from high dose of empagliflozin and the full significance level (5%) will be maintained by the hierarchical procedure.p-value: <0.000195% CI: [-126.01, -44.97]ANCOVA