Diabetes Mellitus, Type 2
Conditions
Brief summary
To investigate efficacy, safety and tolerability of BI 1356 versus placebo
Interventions
DRUGlinagliptin
active
DRUGplacebo
placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients with type 2 diabetes and insufficient glycaemic control. * Age 18 or over and not older than 80 years
Exclusion criteria
* Use of more than one oral antidiabetic agent within 10 weeks prior to informed consent, insulin, glitazones or GLP-1 analogues within 3 months. * Myocardial infarction, stroke or transient ischaemic attack within 6 months prior to informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Change From Baseline at Week 24 | Baseline and week 24 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Change From Baseline at Week 6 | Baseline and week 6 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. |
| HbA1c Change From Baseline at Week 12 | Baseline and week 12 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. |
| HbA1c Change From Baseline at Week 18 | Baseline and week 18 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. |
| FPG Change From Baseline at Week 24 | Baseline and week 24 | This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. |
| FPG Change From Baseline at Week 6 | Baseline and week 6 | This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. |
| FPG Change From Baseline at Week 12 | Baseline and week 12 | This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. |
| Percentage of Patients With HbA1c<7.0% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 7.0%. |
| Percentage of Patients With HbA1c <7.0% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 7.0%. Only patients with baseline HbA1c \>= 7% |
| Percentage of Patients With HbA1c <6.5% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 6.5%. Only patients with baseline HbA1c \>= 6.5%. |
| Percentage of Patients With HbA1c<6.5% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 6.5%. |
| Percentage of Patients With HbA1c Lowering by 0.5% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c reduction from baseline \>= 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%. |
| Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24 | Baseline and week 24 | This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline PPG and previous anti-diabetic medication. |
| FPG Change From Baseline at Week 18 | Baseline and week 18 | This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. |
Countries
Croatia, India, Israel, Italy, Malaysia, Netherlands, Poland, Romania, Slovakia, Thailand, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients randomized to receive treatment with matching placebo | 167 |
| Linagliptin Patients randomized to receive treatment with Linagliptin 5mg | 336 |
| Total | 503 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other incl. lack of efficacy | 6 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Placebo | Linagliptin | Total |
|---|---|---|---|
| Age, Continuous | 54.4 Years STANDARD_DEVIATION 10.3 | 56.4 Years STANDARD_DEVIATION 10.1 | 55.7 Years STANDARD_DEVIATION 10.2 |
| Body Mass Index (BMI) continuous | 29.08 kg/m^2 STANDARD_DEVIATION 4.84 | 29.04 kg/m^2 STANDARD_DEVIATION 4.8 | 29.05 kg/m^2 STANDARD_DEVIATION 4.81 |
| Fasting plasma glucose (FPG) | 168.7 mg/dL STANDARD_DEVIATION 39.3 | 164.7 mg/dL STANDARD_DEVIATION 41.9 | 166.0 mg/dL STANDARD_DEVIATION 41.1 |
| Glycosylated Hemoglobin A1 (HbA1C) | 8.00 Percent STANDARD_DEVIATION 0.86 | 8.00 Percent STANDARD_DEVIATION 0.87 | 8.00 Percent STANDARD_DEVIATION 0.67 |
| Sex: Female, Male Female | 88 Participants | 172 Participants | 260 Participants |
| Sex: Female, Male Male | 79 Participants | 164 Participants | 243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 167 | 29 / 336 |
| serious Total, serious adverse events | 7 / 167 | 10 / 336 |
Outcome results
Primary
HbA1c Change From Baseline at Week 24
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline and week 24
Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline at Week 24 | 0.25 Percent | Standard Error 0.07 |
| Linagliptin | HbA1c Change From Baseline at Week 24 | -0.44 Percent | Standard Error 0.05 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-0.85, -0.53]ANCOVA
Secondary
Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24
This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline PPG and previous anti-diabetic medication.
Time frame: Baseline and week 24
Population: Meal Tolerance Test (MTT) set (patients with adequate MTT results available at the beginning and end of the randomised treatment period)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24 | 24.87 mg/dL | Standard Error 10.33 |
| Linagliptin | Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24 | -33.51 mg/dL | Standard Error 6.19 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-82.33, -34.43]ANCOVA
Secondary
FPG Change From Baseline at Week 12
This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time frame: Baseline and week 12
Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline at Week 12 | 10.23 mg/dL | Standard Error 2.63 |
| Linagliptin | FPG Change From Baseline at Week 12 | -10.75 mg/dL | Standard Error 1.8 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-27.21, -14.75]ANCOVA
Secondary
FPG Change From Baseline at Week 18
This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time frame: Baseline and week 18
Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline at Week 18 | 13.11 mg/dL | Standard Error 2.82 |
| Linagliptin | FPG Change From Baseline at Week 18 | -7.25 mg/dL | Standard Error 1.93 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-27.05, -13.68]ANCOVA
Secondary
FPG Change From Baseline at Week 24
This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time frame: Baseline and week 24
Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline at Week 24 | 14.84 mg/dL | Standard Error 2.98 |
| Linagliptin | FPG Change From Baseline at Week 24 | -8.47 mg/dL | Standard Error 2.03 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-30.37, -16.26]ANCOVA
Secondary
FPG Change From Baseline at Week 6
This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time frame: Baseline and week 6
Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline at Week 6 | 6.73 mg/dL | Standard Error 2.33 |
| Linagliptin | FPG Change From Baseline at Week 6 | -10.87 mg/dL | Standard Error 1.59 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-23.11, -12.08]ANCOVA
Secondary
HbA1c Change From Baseline at Week 12
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline and week 12
Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline at Week 12 | 0.16 Percent | Standard Error 0.06 |
| Linagliptin | HbA1c Change From Baseline at Week 12 | -0.46 Percent | Standard Error 0.04 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-0.76, -0.47]ANCOVA
Secondary
HbA1c Change From Baseline at Week 18
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline and week 18
Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline at Week 18 | 0.21 Percent | Standard Error 0.07 |
| Linagliptin | HbA1c Change From Baseline at Week 18 | -0.45 Percent | Standard Error 0.05 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-0.82, -0.49]ANCOVA
Secondary
HbA1c Change From Baseline at Week 6
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline and week 6
Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline at Week 6 | 0.09 Percent | Standard Error 0.05 |
| Linagliptin | HbA1c Change From Baseline at Week 6 | -0.37 Percent | Standard Error 0.04 |
Comparison: Linagliptin vs. Placebop-value: <0.000195% CI: [-0.58, -0.34]ANCOVA
Secondary
Percentage of Patients With HbA1c<6.5% at Week 24
The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 6.5%.
Time frame: Baseline and week 24
Population: This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With HbA1c<6.5% at Week 24 | 4.9 Percentage of Patients |
| Linagliptin | Percentage of Patients With HbA1c<6.5% at Week 24 | 10.8 Percentage of Patients |
Secondary
Percentage of Patients With HbA1c <6.5% at Week 24
The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 6.5%. Only patients with baseline HbA1c \>= 6.5%.
Time frame: Baseline and week 24
Population: This population includes the FAS with baseline HbA1c \>= 6.5%. Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Patients With HbA1c <6.5% at Week 24 | 4.9 percentage of patients | 0 |
| Linagliptin | Percentage of Patients With HbA1c <6.5% at Week 24 | 10.6 percentage of patients | 0 |
Comparison: Linagliptin vs. Placebo~The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication.p-value: 0.032395% CI: [1.078, 5.507]Regression, Logistic
Secondary
Percentage of Patients With HbA1c<7.0% at Week 24
The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 7.0%.
Time frame: Baseline and week 24
Population: This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With HbA1c<7.0% at Week 24 | 15.3 percentage of patients |
| Linagliptin | Percentage of Patients With HbA1c<7.0% at Week 24 | 28.2 percentage of patients |
Secondary
Percentage of Patients With HbA1c <7.0% at Week 24
The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c \>= 7.0%. Only patients with baseline HbA1c \>= 7%
Time frame: Baseline and week 24
Population: This population includes the FAS with baseline HbA1c \>= 7.0%. Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Patients With HbA1c <7.0% at Week 24 | 11.6 percentage of patients | 0 |
| Linagliptin | Percentage of Patients With HbA1c <7.0% at Week 24 | 25.2 percentage of patients | 0 |
Comparison: Linagliptin vs. Placebo~The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication.p-value: 0.000695% CI: [1.575, 5.225]Regression, Logistic
Secondary
Percentage of Patients With HbA1c Lowering by 0.5% at Week 24
The percentage of patients with an HbA1c reduction from baseline \>= 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%.
Time frame: Baseline and week 24
Population: The Full Analysis Set (FAS) included all patients with a baseline and at least one on treatment HbA1c measurement available. Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Patients With HbA1c Lowering by 0.5% at Week 24 | 19.0 percentage of patients | 0 |
| Linagliptin | Percentage of Patients With HbA1c Lowering by 0.5% at Week 24 | 47.1 percentage of patients | 0 |
Comparison: Linagliptin vs. Placebo~The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication.p-value: <0.000195% CI: [2.665, 6.755]Regression, Logistic