Diabetes Mellitus, Type 1
Conditions
Brief summary
This open-label study aims to evaluate the impact of BI 10773 treatment on glomerular filtration rate under controlled conditions of euglycaemia and hyperglycaemia in subjects with type 1 diabetes mellitus with or without renal hyperfiltration and to characterize the safety and efficacy of BI 10773 25 mg QD as add-on therapy to insulin in these subjects.
Interventions
DRUGBI 10773
Oral once daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects 18 years of age or older diagnosed with type 1 diabetes mellitus 2. Glycated hemoglobin (HbA1C) of 6.5% to 11.0% and an estimated glomerular filtration rate (eGFR) greater or equal to 60 ml/min/1.73m² at screening 3. Subjects must be either experienced insulin pump users or be on multiple daily injections of any type of insulin
Exclusion criteria
1. Evidence of macroalbuminuria or leukocyte positive urinalysis at screening 2. Any concomitant medication known to interfere with renin-angiotensin-aldosterone system (RAAS) activity or treatment with any other drugs to reduce blood glucose other than insulin 3. History of macrovascular disease or any other disease which would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Baseline and 8 weeks | The primary endpoint is change in glomerular filtration rate (GFR) after 8 weeks of treatment with empagliflozin under controlled conditions of euglycaemia and hyperglycaemia |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Empagliflozin (BI 10773) 25 mg Oral once daily
Empagliflozin 25 mg: Oral once daily | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | discontinued during placebo run-in | 2 |
| Overall Study | not entered | 8 |
Baseline characteristics
| Characteristic | Empagliflozin (BI 10773) 25 mg |
|---|---|
| Age, Continuous | 24.1 years STANDARD_DEVIATION 5 |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 42 |
| serious Total, serious adverse events | 3 / 42 |
Outcome results
Primary
Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia
The primary endpoint is change in glomerular filtration rate (GFR) after 8 weeks of treatment with empagliflozin under controlled conditions of euglycaemia and hyperglycaemia
Time frame: Baseline and 8 weeks
Population: Per protocol set for renal (PPS\_RENAL) consists of all patients who were treated with study drug and had a baseline measurement and evaluable post-dosing renal data under the clamped hyperglycemia condition for the primary endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients (Empagliflozin 25 mg) | Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Euglycaemia | -19.6 mL/min/1.73 m^2 | Standard Error 5.6 |
| All Patients (Empagliflozin 25 mg) | Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Hyperglycaemia | -30.8 mL/min/1.73 m^2 | Standard Error 6.2 |
| Hyperfilterers (Empagliflozin 25 mg) | Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Euglycaemia | -33.4 mL/min/1.73 m^2 | Standard Error 6.2 |
| Hyperfilterers (Empagliflozin 25 mg) | Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Hyperglycaemia | -44.5 mL/min/1.73 m^2 | Standard Error 7.1 |
| Non-hyperfilterers (Empagliflozin 25 mg) | Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Euglycaemia | 9.0 mL/min/1.73 m^2 | Standard Error 5.9 |
| Non-hyperfilterers (Empagliflozin 25 mg) | Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia | Hyperglycaemia | -2.4 mL/min/1.73 m^2 | Standard Error 7.7 |
Comparison: Test of the difference between baseline and end of treatment under euglycaemia condition for all patientsp-value: 0.0011Paired t-test
Comparison: Test the difference between baseline and end of treatment under hyperglycaemia condition for all patientsp-value: <0.0001Paired t-test
Comparison: Test of the difference between baseline and end of treatment under euglycaemia condition for hyperfilterersp-value: <0.0001Paired t-test
Comparison: Test of the difference between baseline and end of treatment under hyperglycaemia condition for hyperfilterersp-value: <0.0001Paired t-test
Comparison: Test of the difference between baseline and end of treatment under euglycaemia condition for non-hyperfilterersp-value: 0.1524Paired t-test
Comparison: Test of the difference between baseline and end of treatment under hyperglycaemia condition for non-filterersp-value: 0.7585Paired t-test