Diabetes Mellitus, Type 2
Conditions
Brief summary
This is a multi-center, randomised, double-blind, placebo-controlled, parallel-group, efficacy and safety study of empagliflozin as add-on to insulin in Japanese patients with Type 2 Diabetes Mellitus with insufficient glycaemic control
Interventions
DRUGEmpagliflozin
DRUGPlacebo
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of type 2 diabetes mellitus * Patients on diet and exercise regimen who are pre-treated with any insulin therapy alone or in combination with 1 oral antidiabetic drug for at least 12 weeks prior to screening * Fasting C-peptide must be \> 0.5 ng/mL * HbA1c at screening in Patients who are treated with insulin alone must be \>=7.5% and \<=10.0% * HbA1c in Patients who are treated with insulin with 1 oral antidiabetic drug (OAD) must be \>=7.0% and \<=9.5% at screening, and \>=7.5% and \<=10.0% at placebo run-in period * Age at informed consent must be \>=20 and \<75 years * BMI at screening must be \>22 and \<=40 kg/m2 * Further inclusion criteria apply
Exclusion criteria
* Patients who experience uncontrolled hyperglycaemia before randomization * Patients who are treated with sulfonylurea whose dose is more than a half of daily maximum approval dose, glucagon-like peptide-1 (GLP-1) analogue, thiazolidinedione and sodium-glucose co-transporter 2 (SGLT-2) inhibitor * Patients with recent cardiovascular and/or stroke events * Patients with hepatic and/or renal dysfunction * Patients who received anti-obesity drugs or other treatment leading to unstable body weight * Patients who have known allergy or hypersensitivity to insulin and/or empagliflozin * Pre-menopausal women who are nursing or pregnant * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment. | Baseline and 16 weeks | The primary endpoint was the change from baseline in HbA1c after 16 weeks of treatment. The term baseline refers to the last observation prior to the administration of any randomised study drug. Means presented are the adjusted means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs) | From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks | Percentage of patients with investigator defined drug-related Adverse Events (AEs) are presented |
Countries
Japan
Participant flow
Recruitment details
After screening, patients who were pre-treated with insulin and 1 oral antidiabetic drug (OAD) underwent a 10-week wash-out period. Then patients proceeded to a 2-week open-label placebo run-in period. Patients who were pre-treated with insulin alone skipped the wash-out period and proceeded to an open-label placebo run-in period.
Pre-assignment details
Patients who successfully completed the periods and who still satisfied the inclusion/exclusion criteria were randomised to the 52-week double- blind treatment period of the study in which they received either 1 of the 2 doses of empagliflozin or placebo in addition to insulin.
Participants by arm
| Arm | Count |
|---|---|
| Empagliflozin 10 mg Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period | 90 |
| Empagliflozin 25 mg Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period | 86 |
| Placebo Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period | 90 |
| Total | 266 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Not Treated | 0 | 3 | 0 |
| Overall Study | Other reason than specified above | 1 | 2 | 1 |
| Overall Study | Patient withdrawal, not due to AE | 3 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Empagliflozin 10 mg | Empagliflozin 25 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 10.7 | 58.3 years STANDARD_DEVIATION 10 | 58.6 years STANDARD_DEVIATION 9.5 | 58.7 years STANDARD_DEVIATION 10 |
| Baseline glycosylated haemoglobin A1c (HbA1c) [%] | 8.70 % of HbA1c STANDARD_DEVIATION 0.68 | 8.83 % of HbA1c STANDARD_DEVIATION 0.66 | 8.74 % of HbA1c STANDARD_DEVIATION 0.72 | 8.75 % of HbA1c STANDARD_DEVIATION 0.69 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 21 Participants | 23 Participants | 29 Participants | 73 Participants |
| Sex: Female, Male Male | 69 Participants | 63 Participants | 61 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 1 / 86 | 0 / 90 |
| other Total, other adverse events | 49 / 90 | 45 / 86 | 48 / 90 |
| serious Total, serious adverse events | 6 / 90 | 9 / 86 | 8 / 90 |
Outcome results
Primary
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment.
The primary endpoint was the change from baseline in HbA1c after 16 weeks of treatment. The term baseline refers to the last observation prior to the administration of any randomised study drug. Means presented are the adjusted means.
Time frame: Baseline and 16 weeks
Population: Full analysis set (FAS) with last observation carried forward at 16 weeks (LOCF)-16; The FAS consisted of all patients in the TS who had a baseline measurement of the primary endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment. | 0.00 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 10 mg | Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment. | -0.92 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 25 mg | Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment. | -1.00 percentage of HbA1c | Standard Error 0.07 |
Comparison: The statistical model was:~Change from baseline in HbA1c after 16 weeks = overall mean + baseline HbA1c + treatment + baseline renal function + type of insulin therapies + random errorp-value: <0.000195% CI: [-1.11, -0.73]ANCOVA
Comparison: The statistical model was: Change from baseline in HbA1c after 16 weeks = overall mean + baseline HbA1c + treatment + baseline renal function + type of insulin therapies + random errorp-value: <0.000195% CI: [-1.18, -0.82]ANCOVA
Secondary
Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs)
Percentage of patients with investigator defined drug-related Adverse Events (AEs) are presented
Time frame: From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
Population: Treated set (TS): TS consisted of all randomised patients who were treated with at least 1 dose of the study drug during the 52-week double blind treatment period. The TS was the basis for safety analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs) | 25.6 Percentage of participants |
| Empagliflozin 10 mg | Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs) | 43.0 Percentage of participants |
| Empagliflozin 25 mg | Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs) | 43.3 Percentage of participants |