Diabetes Mellitus, Type 2
Conditions
Brief summary
This study is conducted to determine the most appropriate therapeutic doses of BI 10773 in Japanese patients with T2DM at first treatment period. The second treatment period is required to obtain sufficient safety data (one-year exposure to BI 10773) in Japanese patients with T2DM according to the ICH E1 guideline.
Interventions
DRUGBI 10773
BI 10773 tablets low dose once a day
Placebo tablets once a day
DRUGPlacebo (mid dose)
Placebo tablets once a day
Placebo tablets once a day
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 80 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 who are: 1. drug-naïve, defined as no antidiabetic drugs for 10 weeks prior to informed consent. 2. pre-treated with one oral antidiabetic drug; the present antidiabetic therapy has to be unchanged for 10 weeks prior to informed consent. * HbA1c at Visit 1a: 1. for patients who are drug naïve: HbA1c \>=7.0 to =\<10.0% 2. for patients treated with one oral antidiabetic drug: HbA1c \>=6.5 to =\<9.0% * HbA1c of \>=7.0% and =\<10% at Visit 2 (start of run-in)
Exclusion criteria
* Uncontrolled hyperglycaemia with a glucose level \>240 mg/dL (\>13.3 mmol/L) after an overnight fast during wash-out/placebo run-in period and confirmed by a second measurement (not on the same day). * Acute coronary syndromes, stroke or transient ischaemic attack within 12 weeks prior to informed consent * Impaired renal function, defined as calculated eGFR \<60 ml/min (MDRD formula) during screening and/or wash-out period and/or run-in phase. * Bariatric surgery within the past 2 years and other gastrointestinal surgeries that induce chronic malabsorption * Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia) * Treatment with anti-obesity drugs (e.g. sibutramine, mazindol) 12 weeks prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c After 12 Weeks of Treatment. | baseline and 12 weeks | The primary endpoint in this study is the change from baseline in HbA1c after 12 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FPG | baseline and 12 weeks | Change from baseline in FPG after 12 weeks of treatment |
| Occurrence of Treat to Target Efficacy Response | baseline and 12 weeks | Occurrence of treat to target efficacy response, that is an HbA1c of \<7.0% after 12 weeks of treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Hypoglycaemic Adverse Events | between first drug intake of study medication up to a period of 7 days (inclusive) after the last drug intake of study medication, up to 392 days | Number of patients with confirmed hypoglycaemic adverse events |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (12 Week) Placebo once daily group in the 12-week first treatment period | 109 |
| Empa 5mg (12 Week) Empagliflozin 5 mg once daily group in the 12-week first treatment period | 110 |
| Empa 10mg (12 Week) Empagliflozin 10 mg once daily group in the 12-week first treatment period | 109 |
| Empa 25mg (12 Week) Empagliflozin 25 mg once daily group in the 12-week first treatment period | 109 |
| Empa 50mg (12 Week) Empagliflozin 50 mg once daily group in the 12-week first treatment period | 110 |
| Total | 547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| 0-12 Weeks | Adverse Event | 6 | 0 | 1 | 0 | 0 | 2 | 2 | 0 |
| 0-12 Weeks | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| 0-12 Weeks | Withdrawal by Subject | 3 | 0 | 2 | 0 | 0 | 0 | 1 | 0 |
| 12-52 Weeks | Adverse Event | 1 | 0 | 1 | 2 | 3 | 3 | 1 | 2 |
| 12-52 Weeks | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| 12-52 Weeks | Other reason than above | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| 12-52 Weeks | Withdrawal by Subject | 3 | 0 | 3 | 0 | 0 | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo (12 Week) | Empa 5mg (12 Week) | Empa 10mg (12 Week) | Empa 25mg (12 Week) | Empa 50mg (12 Week) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 8.7 | 57.3 years STANDARD_DEVIATION 11.2 | 57.9 years STANDARD_DEVIATION 9.4 | 57.2 years STANDARD_DEVIATION 9.7 | 56.6 years STANDARD_DEVIATION 10.3 | 57.5 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 32 Participants | 25 Participants | 25 Participants | 137 Participants |
| Sex: Female, Male Male | 80 Participants | 84 Participants | 77 Participants | 84 Participants | 85 Participants | 410 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 109 | 19 / 110 | 16 / 109 | 26 / 109 | 20 / 110 | 39 / 109 | 49 / 109 | 83 / 267 | 93 / 265 |
| serious Total, serious adverse events | 3 / 109 | 0 / 110 | 0 / 109 | 3 / 109 | 1 / 110 | 3 / 109 | 8 / 109 | 8 / 267 | 15 / 265 |
Outcome results
Primary
Change From Baseline in HbA1c After 12 Weeks of Treatment.
The primary endpoint in this study is the change from baseline in HbA1c after 12 weeks of treatment.
Time frame: baseline and 12 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (12 Week) | Change From Baseline in HbA1c After 12 Weeks of Treatment. | 0.30 percentage of HbA1c | Standard Error 0.09 |
| Empa 5mg (12 Week) | Change From Baseline in HbA1c After 12 Weeks of Treatment. | -0.42 percentage of HbA1c | Standard Error 0.09 |
| Empa 10mg (12 Week) | Change From Baseline in HbA1c After 12 Weeks of Treatment. | -0.40 percentage of HbA1c | Standard Error 0.09 |
| Empa 25mg (12 Week) | Change From Baseline in HbA1c After 12 Weeks of Treatment. | -0.65 percentage of HbA1c | Standard Error 0.09 |
| Empa 50mg (12 Week) | Change From Baseline in HbA1c After 12 Weeks of Treatment. | -0.61 percentage of HbA1c | Standard Error 0.09 |
Comparison: Difference calculated as empa 5mg minus placebop-value: <0.000195% CI: [-0.87, -0.57]ANCOVA
Comparison: Difference calculated as empa 10mg minus placebop-value: <0.000195% CI: [-0.85, -0.55]ANCOVA
Comparison: Difference calculated as empa 25mg minus placebop-value: <0.000195% CI: [-1.1, -0.8]ANCOVA
Comparison: Difference calculated as empa 50mg minus placebop-value: <0.000195% CI: [-1.06, -0.76]ANCOVA
Secondary
Change From Baseline in FPG
Change from baseline in FPG after 12 weeks of treatment
Time frame: baseline and 12 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (12 Week) | Change From Baseline in FPG | 4.06 mg/dL | Standard Error 2.88 |
| Empa 5mg (12 Week) | Change From Baseline in FPG | -22.65 mg/dL | Standard Error 2.97 |
| Empa 10mg (12 Week) | Change From Baseline in FPG | -25.28 mg/dL | Standard Error 2.77 |
| Empa 25mg (12 Week) | Change From Baseline in FPG | -33.70 mg/dL | Standard Error 2.92 |
| Empa 50mg (12 Week) | Change From Baseline in FPG | -32.54 mg/dL | Standard Error 2.97 |
Comparison: Difference calculated as empa 5mg minus placebop-value: <0.000195% CI: [-31.61, -21.8]ANCOVA
Comparison: Difference calculated as empa 10mg minus placebop-value: <0.000195% CI: [-34.25, -24.42]ANCOVA
Comparison: Difference calculated as empa 25mg minus placebop-value: <0.000195% CI: [-42.66, -32.84]ANCOVA
Comparison: Difference calculated as empa 50mg minus placebop-value: <0.000195% CI: [-41.51, -31.69]ANCOVA
Secondary
Occurrence of Treat to Target Efficacy Response
Occurrence of treat to target efficacy response, that is an HbA1c of \<7.0% after 12 weeks of treatment
Time frame: baseline and 12 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (12 Week) | Occurrence of Treat to Target Efficacy Response | 2.8 percentage of participants |
| Empa 5mg (12 Week) | Occurrence of Treat to Target Efficacy Response | 26.2 percentage of participants |
| Empa 10mg (12 Week) | Occurrence of Treat to Target Efficacy Response | 19.0 percentage of participants |
| Empa 25mg (12 Week) | Occurrence of Treat to Target Efficacy Response | 32.1 percentage of participants |
| Empa 50mg (12 Week) | Occurrence of Treat to Target Efficacy Response | 32.7 percentage of participants |
Comparison: Odds ratio calculated as the odds of Empa 5mg divided by the odds of placebop-value: <0.000195% CI: [5.34, 70.236]Regression, Logistic
Comparison: Odds ratio calculated as the odds of Empa 10mg divided by the odds of placebop-value: 0.000395% CI: [2.942, 40.301]Regression, Logistic
Comparison: Odds ratio calculated as the odds of Empa 25mg divided by the odds of placebop-value: <0.000195% CI: [7.601, 99.99]Regression, Logistic
Comparison: Odds ratio calculated as the odds of Empa 50mg divided by the odds of placebop-value: <0.000195% CI: [12.12, 99.99]Regression, Logistic
Other Pre-specified
Confirmed Hypoglycaemic Adverse Events
Number of patients with confirmed hypoglycaemic adverse events
Time frame: between first drug intake of study medication up to a period of 7 days (inclusive) after the last drug intake of study medication, up to 392 days
Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (12 Week) | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| Empa 5mg (12 Week) | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| Empa 10mg (12 Week) | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| Empa 25mg (12 Week) | Confirmed Hypoglycaemic Adverse Events | 1 participants |
| Empa 50mg (12 Week) | Confirmed Hypoglycaemic Adverse Events | 1 participants |