Diabetes Mellitus, Type 2, Renal Insufficiency
Conditions
Brief summary
This study will investigate the efficacy and safety of the BI 10773 in type 2 diabetic patients with renal impairment in order to provide these data for approval for BI 10773 as an antidiabetic agent by regulatory authorities.
Interventions
DRUGBI 10773
BI 10773 tablets once daily
DRUGPlacebo
Placebo tablets identical to BI 10773 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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of type 2 diabetes mellitus prior to informed consent and an estimated glomerular filtration rate of \<90 ml/min. 2. Male and female patients on diet and exercise regimen who are pre-treated with any antidiabetic therapy and are on the maximum tolerated dose which has been unchanged for 12 weeks prior to randomisation. 3. HbA1c greater than or equal to 7.0% and less than or equal to 10.0% . 4. Aged 18 years or above. 5. Body Mass Index less than or equal to 45 kg/m2
Exclusion criteria
1. Uncontrolled hyperglycaemia defined as \>13.3 mmol/L after an overnight fast during placebo run-in. 2. Impaired renal function, defined as an estimated glomerular filtration rate \<15 ml/min. 3. Renal impairment requiring any form of chronic dialysis. 4. Requiring acute dialysis within three months prior to informed consent. 5. Renal transplant recipient. 6. Myocardial infarction, stroke or Transient Ischemic Attack within three months prior to informed consent. 7. Indication of liver disease. 8. Bariatric surgery within the past two years. 9. Medical history of cancer. 10. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cell. 11. Contraindications to pre-existing background antidiabetic therapy. 12. Treatment with anti-obesity drugs. 13. Current treatment with systemic steroids or change in dosage of thyroid hormones within six weeks prior to informed consent or any other uncontrolled endocrine disorder except Type 2 Diabetes. 14. Pre-menopausal women who are nursing or pregnant or are of child-bearing potential and are not practising an acceptable method of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Change From Baseline in Patients With Mild or Moderate Renal Impairment | Baseline and 24 weeks | Change from baseline in HbA1c after 24 weeks, for patients with mild or moderate renal impairment. Note adjusted means are provided. |
| HbA1c Change From Baseline in Patients With Mild Renal Impairment | Baseline and 24 weeks | Change from baseline in HbA1c after 24 weeks, for patients with mild renal impairment. Note adjusted means are provided. |
| HbA1c Change From Baseline in Patients With Moderate Renal Impairment | Baseline and 24 weeks | Change from baseline in HbA1c after 24 weeks, for patients with moderate renal impairment. Note adjusted means are provided. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycaemic Events | From first drug administration until 7 days after last trial medication intake, up to 458 days | Percentage of patients who experienced a hypoglycaemic event. A hypoglycaemic event was regarded as confirmed if it was documented as an adverse event with plasma glucose values \<= 70 mg/dL (\<=3.9mmol/L) measured or with a documentation that the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative action had been required. |
Countries
Canada, France, Hong Kong, India, Malaysia, Netherlands, Philippines, Poland, Portugal, Russia, Slovakia, South Africa, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | 319 |
| Empa 10mg Single oral dose of empagliflozin (empa) 10mg plus a placebo tablet matching the 25mg empa dose were taken once daily for 52 weeks. | 98 |
| Empa 25mg Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. | 321 |
| Total | 738 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 18 | 4 | 21 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 | 3 |
| Overall Study | Non compliant with protocol | 1 | 1 | 4 |
| Overall Study | Not treated | 2 | 0 | 1 |
| Overall Study | Other reason not defined above | 9 | 1 | 4 |
| Overall Study | Patient refusal to continue,not due toAE | 10 | 4 | 8 |
Baseline characteristics
| Characteristic | Total | Placebo | Empa 10mg | Empa 25mg |
|---|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 8.8 | 64.1 years STANDARD_DEVIATION 8.7 | 63.2 years STANDARD_DEVIATION 8.5 | 63.9 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 308 Participants | 138 Participants | 38 Participants | 132 Participants |
| Sex: Female, Male Male | 430 Participants | 181 Participants | 60 Participants | 189 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 | 207 / 319 | 64 / 98 | 187 / 321 |
| serious Total, serious adverse events | 44 / 319 | 6 / 98 | 40 / 321 |
Outcome results
Primary
HbA1c Change From Baseline in Patients With Mild or Moderate Renal Impairment
Change from baseline in HbA1c after 24 weeks, for patients with mild or moderate renal impairment. Note adjusted means are provided.
Time frame: Baseline and 24 weeks
Population: Full analysis set (FAS) which included all randomised patients, treated with at least one dose of trial medication, who had a baseline HbA1c value. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline in Patients With Mild or Moderate Renal Impairment | 0.05 percentage of HbA1c | Standard Error 0.04 |
| Empa 25mg | HbA1c Change From Baseline in Patients With Mild or Moderate Renal Impairment | -0.46 percentage of HbA1c | Standard Error 0.04 |
p-value: <0.000195% CI: [-0.62, -0.39]ANCOVA
Primary
HbA1c Change From Baseline in Patients With Mild Renal Impairment
Change from baseline in HbA1c after 24 weeks, for patients with mild renal impairment. Note adjusted means are provided.
Time frame: Baseline and 24 weeks
Population: Full analysis set (FAS) which included all randomised patients, treated with at least one dose of trial medication, who had a baseline HbA1c value. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline in Patients With Mild Renal Impairment | 0.06 percentage of HbA1c | Standard Error 0.07 |
| Empa 25mg | HbA1c Change From Baseline in Patients With Mild Renal Impairment | -0.46 percentage of HbA1c | Standard Error 0.07 |
| Empa 25mg | HbA1c Change From Baseline in Patients With Mild Renal Impairment | -0.63 percentage of HbA1c | Standard Error 0.07 |
p-value: <0.000195% CI: [-0.88, -0.49]ANCOVA
p-value: <0.000195% CI: [-0.72, -0.32]ANCOVA
Primary
HbA1c Change From Baseline in Patients With Moderate Renal Impairment
Change from baseline in HbA1c after 24 weeks, for patients with moderate renal impairment. Note adjusted means are provided.
Time frame: Baseline and 24 weeks
Population: Full analysis set (FAS) which included all randomised patients, treated with at least one dose of trial medication, who had a baseline HbA1c value. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline in Patients With Moderate Renal Impairment | 0.05 percentage of HbA1c | Standard Error 0.05 |
| Empa 25mg | HbA1c Change From Baseline in Patients With Moderate Renal Impairment | -0.37 percentage of HbA1c | Standard Error 0.05 |
p-value: <0.000195% CI: [-0.56, -0.28]ANCOVA
Other Pre-specified
Hypoglycaemic Events
Percentage of patients who experienced a hypoglycaemic event. A hypoglycaemic event was regarded as confirmed if it was documented as an adverse event with plasma glucose values \<= 70 mg/dL (\<=3.9mmol/L) measured or with a documentation that the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative action had been required.
Time frame: From first drug administration until 7 days after last trial medication intake, up to 458 days
Population: Treated set which included all patients treated with at least one dose of randomised trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Hypoglycaemic Events | 27.6 percentage of participants |
| Empa 25mg | Hypoglycaemic Events | 26.5 percentage of participants |
| Empa 25mg | Hypoglycaemic Events | 27.4 percentage of participants |