Diabetes Mellitus, Type 1
Conditions
Brief summary
Placebo-controlled, double blind (triple-dummy technique), randomised parallel design comparison of three oral doses (2.5 mg, 10 mg, and 25 mg) of empagliflozin in patients with T1DM as adjunctive therapy to insulin over 28 days. Patients will undergo a 14-day open-label placebo run-in period before randomisation. Background insulin therapy will be kept stable during the first 7 days of the treatment period and will be freely adjusted thereafter.
Interventions
DRUGEmpagliflozin medium
Empagliflozin medium
DRUGEmpagliflozin low
Empagliflozin low
Empagliflozin high
DRUGEmpagliflozin high placebo
Empagliflozin high placebo
DRUGEmpagliflozin medium placebo
Empagliflozin medium placebo
DRUGEmpagliflozin low placebo
Empagliflozin low placebo
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent * Male or female patient receiving insulin for treatment of T1DM for at least 12 months * C-peptide \< 1.5 ng/mL * Age 18 to 65 years * HbA1c of 7.5% to 10.5% * Multiple daily injections (MDI) of any type of insulin * Willing to follow an established and individualized carbohydrate counting method and an insulin administration algorithm * Body Mass Index of 18.5 to 35.0 kg/m2 * Estimated glomerular filtration rate 60 to 150 mL/min/1.73 m² * Able and willing to perform study assessments according to investigator's judgement * Compliance with trial drug administration 80% to 120% during run-in period * Willing not to take any paracetamol containing drugs during the trial
Exclusion criteria
* Acute symptomatic urinary tract infection or genital infection, chronic or recurrent cystitis * History of type 2 diabetes mellitus, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis * Pancreas, pancreatic islet cells or renal transplant recipient * Type 1 diabetes mellitus treatment with any other antihyperglycaemic drug except insulin within last 3 months or history of clinically relevant hypersensitivity * Occurrence of hypoglycaemia that required hospitalization or treatment by an emergency physician or paramedic within last 3 months * Hypoglycaemia unawareness or frequent episodes of unexplained hypoglycaemia * Occurrence of diabetic ketoacidosis that required hospitalization or treatment by an emergency physician or paramedic within last 12 months * History of macrovascular disease including cardiovascular, cerebrovascular and peripheral artery disease * Autonomic neuropathy with gastroparesis * Brittle diabetes * Liver disease * Treatment with anti-obesity drugs, surgery or aggressive diet regimen leading to unstable body weight * Treatment with systemic corticosteroids * Change in dose of thyroid hormones within last 6 weeks or planned change or initiation of such a therapy * Medical history of cancer or treatment for cancer in the last five years * Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells * Alcohol or drug abuse that would interfere with trial participation or any ongoing clinical condition that would jeopardize patient's or site personnel's safety or study compliance * Intake of an investigational drug in another trial within last 30 days * Not able to understand and comply with study requirements * Pre-menopausal women who are nursing or pregnant or of child-bearing potential and are not practising an acceptable method of birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo | baseline (Day -1) and 7 days after first drug administration (Day 7) | Change of urinary glucose excretion (UGE) (g/24 h) from baseline (refers to the last measurement prior to the first intake of any randomised trial medication) after seven days of treatment with empagliflozin 2.5 mg, 10 mg, or 25 mg, or placebo. The treatment effect was estimated on the basis of the least square mean treatment difference at Day 7 extracted from the primary analysis model. The primary endpoint is exploratory. |
Countries
Austria, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet; oral administration once daily | 19 |
| Empagliflozin 2.5 mg Empagliflozin 2.5 mg tablet; oral administration once daily | 19 |
| Empagliflozin 10 mg Empagliflozin 10 mg tablet; oral administration once daily | 19 |
| Empagliflozin 25 mg Empagliflozin 25 mg tablet; oral administration once daily | 18 |
| Total | 75 |
Baseline characteristics
| Characteristic | Placebo | Empagliflozin 2.5 mg | Empagliflozin 10 mg | Empagliflozin 25 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 10.6 | 41.9 years STANDARD_DEVIATION 12.4 | 39.6 years STANDARD_DEVIATION 11.6 | 41.9 years STANDARD_DEVIATION 9.7 | 41.0 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 4 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Male | 13 Participants | 15 Participants | 15 Participants | 10 Participants | 53 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 | 17 / 19 | 17 / 19 | 15 / 19 | 18 / 18 |
| serious Total, serious adverse events | 1 / 19 | 0 / 19 | 0 / 19 | 0 / 18 |
Outcome results
Primary
Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo
Change of urinary glucose excretion (UGE) (g/24 h) from baseline (refers to the last measurement prior to the first intake of any randomised trial medication) after seven days of treatment with empagliflozin 2.5 mg, 10 mg, or 25 mg, or placebo. The treatment effect was estimated on the basis of the least square mean treatment difference at Day 7 extracted from the primary analysis model. The primary endpoint is exploratory.
Time frame: baseline (Day -1) and 7 days after first drug administration (Day 7)
Population: Full analysis set (FAS): all patients randomised, treated with at least one dose of study drug, had a baseline UGE (g/24 h) and a UGE (g/24 h) on Day 1 or Day 7.~The last observation carried forward (LOCF) approach was used as the primary method of imputation for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo | -3.56 g/24h | Standard Error 4.27 |
| Empagliflozin 2.5 mg | Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo | 72.45 g/24h | Standard Error 7.01 |
| Empagliflozin 10 mg | Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo | 103.33 g/24h | Standard Error 6.68 |
| Empagliflozin 25 mg | Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo | 101.79 g/24h | Standard Error 6.51 |
Comparison: Comparison of Empagliflozin 2.5 mg with Placebop-value: <0.000195% CI: [58.6, 93.59]ANCOVA
Comparison: Comparison of Empagliflozin 10 mg with Placebop-value: <0.000195% CI: [88.73, 124.05]ANCOVA
Comparison: Comparison of Empagliflozin 25 mg with Placebop-value: <0.000195% CI: [86.88, 122.74]ANCOVA