Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of this study is to investigate the effect of BI 1356 on 24-h glucose control and various pharmacodynamic parameters in type 2 diabetic patients with inadequate glycaemic control.
Interventions
DRUGPlacebo (linagliptin)
once daily for 28 days
DRUGSitagliptin
100 mg once daily for 28 days
once daily for 28 days
DRUGLinagliptin
5mg once daily for 28 days
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 and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with not more than one drug * Glycosylated haemoglobin A1 (HbA1c) 6.5 to 10.0% at Start of Run-in
Exclusion criteria
* Myocardial infarction, stroke or transient ischemic attack TIA within 6 months prior to informed consent * Impaired hepatic function * Renal insufficiency with a creatinine clearance \< 50 mL/min * Treatment with rosiglitazone, pioglitazone, glucagon like peptide 1 (GLP-1) analogues, insulin, dipeptidyl peptidase 4 (DPP-4) inhibitors or anti-obesity drugs 3 months prior to informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean Glucose (WMG) Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 WMG value minus the baseline WMG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication, and baseline WMG. |
| GLP-1 (Glucagon Like Peptide 1) AUEC (0-2h) (Area Under Effect Curve) Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 GLP-1 AUEC (0-2h) value minus the baseline GLP-1 AUEC (0-2h) value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline GLP-1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose (FPG) Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 FPG value minus the baseline FPG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline FPG. |
| Plasma Glucose Area Under Effect Curve (AUEC) (0-3h) Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 Glucose AUEC (0-3h) value minus the baseline Glucose AUEC (0-3h) value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline plasma glucose AUEC (0-3h). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Sensitivity Analysis of the WMG Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 WMG value minus the baseline WMG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline WMG. |
| Exploratory Sensitivity Analysis of GLP-1 AUEC (0-2h) Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 GLP-1 AUEC (0-2h) value minus the baseline GLP-1 AUEC (0-2h) value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline GLP-1. |
| Exploratory Sensitivity Analysis of FPG Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 FPG value minus the baseline FPG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline FPG. |
| Exploratory Sensitivity Analysis of Plasma Glucose AUEC (0-3h) Change From Baseline at Day 28 | Baseline and day 28 | The change from baseline reflects the day 28 FPG value minus the baseline FPG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline FPG. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients randomized to receive treatment with matching placebo | 40 |
| BI1356 Patients randomized to receive treatment with BI1356 5 mg | 40 |
| Sitagliptin Patients randomized to receive treatment with Sitagliptin 100 mg | 41 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Other incl. Lack of Efficacy | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | BI1356 | Sitagliptin | Placebo |
|---|---|---|---|---|
| Age, Continuous | 61.1 Years STANDARD_DEVIATION 9.14 | 60.7 Years STANDARD_DEVIATION 10.11 | 62.0 Years STANDARD_DEVIATION 7.85 | 60.5 Years STANDARD_DEVIATION 9.5 |
| Body Mass Index (BMI) continuous | 30.8 kg/m^2 STANDARD_DEVIATION 4.29 | 31.4 kg/m^2 STANDARD_DEVIATION 4.48 | 30.7 kg/m^2 STANDARD_DEVIATION 4.56 | 30.3 kg/m^2 STANDARD_DEVIATION 3.83 |
| Fasting plasma glucose (FPG) continuous | 166.6 mg/dL STANDARD_DEVIATION 27.55 | 166.9 mg/dL STANDARD_DEVIATION 27.65 | 160.3 mg/dL STANDARD_DEVIATION 25.35 | 172.8 mg/dL STANDARD_DEVIATION 28.81 |
| Glycosylated Hemoglobin A1 (HbA1C) continuous | 7.32 Percent STANDARD_DEVIATION 0.53 | 7.32 Percent STANDARD_DEVIATION 0.59 | 7.17 Percent STANDARD_DEVIATION 0.44 | 7.47 Percent STANDARD_DEVIATION 0.53 |
| Sex: Female, Male Female | 35 Participants | 15 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Male | 86 Participants | 25 Participants | 32 Participants | 29 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 | 5 / 40 | 5 / 40 | 6 / 41 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 41 |
Outcome results
Primary
GLP-1 (Glucagon Like Peptide 1) AUEC (0-2h) (Area Under Effect Curve) Change From Baseline at Day 28
The change from baseline reflects the day 28 GLP-1 AUEC (0-2h) value minus the baseline GLP-1 AUEC (0-2h) value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline GLP-1.
Time frame: Baseline and day 28
Population: The pharmacodynamic set(PD-set) consisted of all randomised patients who were treated with at least one dose of study drug. Analysis was based upon model with only BI 1356 and Placebo groups, further restricted to patients who had a baseline and at least one ontreatment value for GLP-1. Sitagliptin results are from model containing all 3 groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | GLP-1 (Glucagon Like Peptide 1) AUEC (0-2h) (Area Under Effect Curve) Change From Baseline at Day 28 | 0.4 pmol*h/L | Standard Error 2.1 |
| BI1356 | GLP-1 (Glucagon Like Peptide 1) AUEC (0-2h) (Area Under Effect Curve) Change From Baseline at Day 28 | 18.5 pmol*h/L | Standard Error 2.1 |
| Sitagliptin | GLP-1 (Glucagon Like Peptide 1) AUEC (0-2h) (Area Under Effect Curve) Change From Baseline at Day 28 | 15.3 pmol*h/L | Standard Error 2 |
Comparison: BI1356 minus Placebop-value: <0.000195% CI: [12.4, 23.9]ANCOVA
Primary
Weighted Mean Glucose (WMG) Change From Baseline at Day 28
The change from baseline reflects the day 28 WMG value minus the baseline WMG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication, and baseline WMG.
Time frame: Baseline and day 28
Population: The pharmacodynamic set(PD-set) consisted of all randomised patients who were treated with at least one dose of study drug. This analysis was based upon model with only BI 1356 and Placebo groups, further restricted to patients who had a baseline and at least one on-treatment value for WMG. Sitagliptin results are from model containing all 3 groups
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean Glucose (WMG) Change From Baseline at Day 28 | 0.1 mg/dL | Standard Error 3 |
| BI1356 | Weighted Mean Glucose (WMG) Change From Baseline at Day 28 | -19.8 mg/dL | Standard Error 2.9 |
| Sitagliptin | Weighted Mean Glucose (WMG) Change From Baseline at Day 28 | -26.1 mg/dL | Standard Error 2.8 |
Comparison: BI1356 minus Placebop-value: <0.000195% CI: [-28, -11.9]ANCOVA
Secondary
Fasting Plasma Glucose (FPG) Change From Baseline at Day 28
The change from baseline reflects the day 28 FPG value minus the baseline FPG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline FPG.
Time frame: Baseline and day 28
Population: The pharmacodynamic set(PD-set) consisted of all randomised patients who were treated with at least one dose of study drug. This analysis was based upon model with only BI 1356 and Placebo groups, further restricted to patients who had a baseline and at least one on-treatment value for FPG. Sitagliptin results are from model containing all 3 groups
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Fasting Plasma Glucose (FPG) Change From Baseline at Day 28 | -0.1 mg/dL | Standard Error 3.6 |
| BI1356 | Fasting Plasma Glucose (FPG) Change From Baseline at Day 28 | -10.9 mg/dL | Standard Error 3.5 |
| Sitagliptin | Fasting Plasma Glucose (FPG) Change From Baseline at Day 28 | -15.6 mg/dL | Standard Error 3.1 |
Comparison: BI1356 minus Placebop-value: 0.028395% CI: [-20.4, -1.2]ANCOVA
Secondary
Plasma Glucose Area Under Effect Curve (AUEC) (0-3h) Change From Baseline at Day 28
The change from baseline reflects the day 28 Glucose AUEC (0-3h) value minus the baseline Glucose AUEC (0-3h) value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline plasma glucose AUEC (0-3h).
Time frame: Baseline and day 28
Population: The pharmacodynamic set (PD-set) consisted of all randomised patients who were treated with at least one dose of study drug. This analysis was based upon model with only BI 1356 and Placebo, further restricted to patients who had a baseline and at least one on-treatment value for Glucose AUEC(0-3h). Sitagliptin results from model with all 3 groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Glucose Area Under Effect Curve (AUEC) (0-3h) Change From Baseline at Day 28 | 8.1 mg*h/dL | Standard Error 15.1 |
| BI1356 | Plasma Glucose Area Under Effect Curve (AUEC) (0-3h) Change From Baseline at Day 28 | -98.4 mg*h/dL | Standard Error 14.7 |
| Sitagliptin | Plasma Glucose Area Under Effect Curve (AUEC) (0-3h) Change From Baseline at Day 28 | -119.1 mg*h/dL | Standard Error 13.3 |
Comparison: BI1356 minus Placebop-value: <0.000195% CI: [-147, -66]ANCOVA
Other Pre-specified
Exploratory Sensitivity Analysis of FPG Change From Baseline at Day 28
The change from baseline reflects the day 28 FPG value minus the baseline FPG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline FPG.
Time frame: Baseline and day 28
Population: This analysis was based upon the PD-set further restricted to patients who had a baseline and at least one on-treatment value for FPG.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Exploratory Sensitivity Analysis of FPG Change From Baseline at Day 28 | 0.4 mg/dL | Standard Error 3.2 |
| BI1356 | Exploratory Sensitivity Analysis of FPG Change From Baseline at Day 28 | -10.3 mg/dL | Standard Error 3.1 |
| Sitagliptin | Exploratory Sensitivity Analysis of FPG Change From Baseline at Day 28 | -15.6 mg/dL | Standard Error 3.1 |
Comparison: BI 1356 minus Sitagliptin. This analysis comparing BI1356 to Sitagliptin was conducted as an exploratory analysis at the time of analysing the study data. The study was not powered for such a comparison.p-value: 0.228195% CI: [-3.3, 13.8]ANCOVA
Other Pre-specified
Exploratory Sensitivity Analysis of GLP-1 AUEC (0-2h) Change From Baseline at Day 28
The change from baseline reflects the day 28 GLP-1 AUEC (0-2h) value minus the baseline GLP-1 AUEC (0-2h) value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline GLP-1.
Time frame: Baseline and day 28
Population: This analysis was based upon the PD-set further restricted to patients who had a baseline and at least one on-treatment value for GLP-1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Exploratory Sensitivity Analysis of GLP-1 AUEC (0-2h) Change From Baseline at Day 28 | -0.1 pmol*h/L | Standard Error 2 |
| BI1356 | Exploratory Sensitivity Analysis of GLP-1 AUEC (0-2h) Change From Baseline at Day 28 | 18.1 pmol*h/L | Standard Error 2 |
| Sitagliptin | Exploratory Sensitivity Analysis of GLP-1 AUEC (0-2h) Change From Baseline at Day 28 | 15.3 pmol*h/L | Standard Error 2 |
Comparison: BI 1356 minus Sitagliptin. This analysis comparing BI1356 to Sitagliptin was conducted as an exploratory analysis at the time of analysing the study data. The study was not powered for such a comparison.p-value: 0.31395% CI: [-2.7, 8.2]ANCOVA
Other Pre-specified
Exploratory Sensitivity Analysis of Plasma Glucose AUEC (0-3h) Change From Baseline at Day 28
The change from baseline reflects the day 28 FPG value minus the baseline FPG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline FPG.
Time frame: Baseline and day 28
Population: This analysis was based upon the PD-set further restricted to patients who had a baseline and at least one on-treatment value for Plasma Glucose AUEC (0-3h).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Exploratory Sensitivity Analysis of Plasma Glucose AUEC (0-3h) Change From Baseline at Day 28 | 9.8 mg*h/dL | Standard Error 14 |
| BI1356 | Exploratory Sensitivity Analysis of Plasma Glucose AUEC (0-3h) Change From Baseline at Day 28 | -96.4 mg*h/dL | Standard Error 13.5 |
| Sitagliptin | Exploratory Sensitivity Analysis of Plasma Glucose AUEC (0-3h) Change From Baseline at Day 28 | -119.1 mg*h/dL | Standard Error 13.3 |
Comparison: BI 1356 minus Sitagliptin. This analysis comparing BI1356 to Sitagliptin was conducted as an exploratory analysis at the time of analysing the study data. The study was not powered for such a comparison.p-value: 0.22395% CI: [-14, 59.5]ANCOVA
Other Pre-specified
Exploratory Sensitivity Analysis of the WMG Change From Baseline at Day 28
The change from baseline reflects the day 28 WMG value minus the baseline WMG value. Means are treatment adjusted for baseline HbA1c, previous anti-diabetic medication and baseline WMG.
Time frame: Baseline and day 28
Population: This analysis was based upon the PD-set further restricted to patients who had a baseline and at least one on-treatment value for WMG.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Exploratory Sensitivity Analysis of the WMG Change From Baseline at Day 28 | -0.2 mg/dL | Standard Error 2.9 |
| BI1356 | Exploratory Sensitivity Analysis of the WMG Change From Baseline at Day 28 | -20.1 mg/dL | Standard Error 2.8 |
| Sitagliptin | Exploratory Sensitivity Analysis of the WMG Change From Baseline at Day 28 | -26.1 mg/dL | Standard Error 2.8 |
Comparison: BI 1356 minus Sitagliptin. This analysis comparing BI1356 to Sitagliptin was conducted as an exploratory analysis at the time of analysing the study data. The study was not powered for such a comparison.p-value: 0.127495% CI: [-1.7, 13.8]ANCOVA