Diabetes Mellitus, Type 2
Conditions
Brief summary
Efficacy and safety of BI 1356 compared to placebo in patients with type 2 diabetes who have insufficient glycaemic control despite treatment with a sulfonylurea drug.
Interventions
DRUGBI 1356
5mg orally (po) tablet qd
DRUGPlacebo
Placebo matching BI 1356 5mg one tablet daily
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
Patients between 18 and 80 years old with type 2 diabetes and insufficient glycemic control \[glycosylated hemoglobin (HbA1c 7% to 10%)\] despite therapy with a sulfonylurea drug
Exclusion criteria
Myocardial infarction,stroke or transient ischaemic attack in last 6 months Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, insulin or anti-obesity drugs in the past 3 months Impaired hepatic function Severe renal impairment Current treatment with systemic steroids Change in thyroid hormone dosage Hereditary galactose intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18 | Baseline, week 18 | HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 | week 18 | An absolute efficacy response is defined as HbA1c \< 7.0% at 18 weeks. A non-response is defined as HbA1c \>= 7.0% at 18 weeks. |
| Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 | week 18 | An absolute efficacy response is defined as HbA1c \< 6.5% at 18 weeks. A non-response is defined as HbA1c \>= 6.5% at 18 weeks. |
| Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 | Baseline, week 18 | An efficacy response is defined as HbA1c lowered by 0.5% or more at 18 weeks. A non-response is defined as HbA1c not lowered by 0.5% or more at 18 weeks. |
| Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6 | Baseline, week 6 | HbA1c is measured as a percent. The change from baseline reflects the Week 6 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication. |
| Change From Baseline in Fasting Plasma Glucose at Week 18 | Baseline, week 18 | Change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication. |
| Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18 | Baseline, week 18 | HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication. |
| Change From Baseline in Fasting Plasma Glucose at Week 6 | Baseline, week 6 | Change from baseline reflects the Week 6 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication. |
| Change From Baseline in Fasting Plasma Glucose at Week 12 | Baseline, week 12 | Change from baseline reflects the Week 12 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication. |
| Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12 | Baseline, week 12 | HbA1c is measured as a percent. The change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication. |
Countries
Argentina, Hungary, India, Japan, Poland, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo tablet taken orally once daily | 84 |
| Linagliptin 5.0 mg Linagliptin 5.0 mg tablet taken orally once daily | 161 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Linagliptin 5.0 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 9.8 | 56.9 years STANDARD_DEVIATION 9.9 | 56.2 years STANDARD_DEVIATION 10.2 |
| Baseline glycosylated hemoglobin (HbA1c) | 8.61 percentage STANDARD_DEVIATION 0.85 | 8.61 percentage STANDARD_DEVIATION 0.81 | 8.6 percentage STANDARD_DEVIATION 0.72 |
| Body Mass Index (BMI) | 28.40 kilogram/square meter STANDARD_DEVIATION 5.02 | 28.33 kilogram/square meter STANDARD_DEVIATION 5.04 | 28.21 kilogram/square meter STANDARD_DEVIATION 5.12 |
| Fasting blood plasma glucose (FPG) | 182.0 milligram/deciliter (mg/dL) STANDARD_DEVIATION 51.8 | 179.6 milligram/deciliter (mg/dL) STANDARD_DEVIATION 50.9 | 174.9 milligram/deciliter (mg/dL) STANDARD_DEVIATION 49 |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 76 participants | 119 participants | 43 participants |
| Race/Ethnicity, Customized Black | 11 participants | 17 participants | 6 participants |
| Race/Ethnicity, Customized Hispanic | 28 participants | 42 participants | 14 participants |
| Race/Ethnicity, Customized Not Hispanic | 133 participants | 203 participants | 70 participants |
| Race/Ethnicity, Customized White | 73 participants | 107 participants | 34 participants |
| Sex: Female, Male Female | 84 Participants | 116 Participants | 32 Participants |
| Sex: Female, Male Male | 77 Participants | 129 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 84 | 14 / 161 |
| serious Total, serious adverse events | 1 / 84 | 5 / 161 |
Outcome results
Primary
Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18
HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline, week 18
Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of HbA1c. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18 | -0.07 percent | Standard Error 0.1 |
| Linagliptin 5.0 mg | Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18 | -0.54 percent | Standard Error 0.07 |
Comparison: Linagliptin 5.0 mg versus placebop-value: <0.000195% CI: [-0.7, -0.24]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 12
Change from baseline reflects the Week 12 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.
Time frame: Baseline, week 12
Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of FPG. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose at Week 12 | 4.1 mg/dL | Standard Error 4.7 |
| Linagliptin 5.0 mg | Change From Baseline in Fasting Plasma Glucose at Week 12 | -10.3 mg/dL | Standard Error 3.4 |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.010595% CI: [-25.5, -3.4]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 18
Change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.
Time frame: Baseline, week 18
Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of FPG. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose at Week 18 | -1.8 mg/dL | Standard Error 4.5 |
| Linagliptin 5.0 mg | Change From Baseline in Fasting Plasma Glucose at Week 18 | -8.2 mg/dL | Standard Error 3.3 |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.240695% CI: [-17.2, 4.3]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 6
Change from baseline reflects the Week 6 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.
Time frame: Baseline, week 6
Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of FPG. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose at Week 6 | -7.6 mg/dL | Standard Error 3.8 |
| Linagliptin 5.0 mg | Change From Baseline in Fasting Plasma Glucose at Week 6 | -13.5 mg/dL | Standard Error 2.7 |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.19795% CI: [-14.9, 3.1]ANCOVA
Secondary
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12
HbA1c is measured as a percent. The change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline, week 12
Population: FAS patients. Mixed Model Repeated Measurements (MMRM) analysis of Observed Cases (OC).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12 | -0.11 percent | Standard Error 0.09 |
| Linagliptin 5.0 mg | Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12 | -0.61 percent | Standard Error 0.07 |
Comparison: Linagliptin 5.0 mg versus placebop-value: <0.000195% CI: [-0.72, -0.276]Mixed Models Analysis
Secondary
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18
HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline, week 18
Population: FAS patients. Mixed Model Repeated Measurements (MMRM) analysis of Observed Cases (OC).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18 | -0.08 percent | Standard Error 0.1 |
| Linagliptin 5.0 mg | Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18 | -0.55 percent | Standard Error 0.07 |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.000295% CI: [-0.716, -0.226]Mixed Models Analysis
Secondary
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6
HbA1c is measured as a percent. The change from baseline reflects the Week 6 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Time frame: Baseline, week 6
Population: FAS patients. Mixed Model Repeated Measurements (MMRM) analysis of Observed Cases (OC).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6 | -0.02 percent | Standard Error 0.07 |
| Linagliptin 5.0 mg | Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6 | -0.43 percent | Standard Error 0.05 |
Comparison: Linagliptin 5.0 mg versus placebop-value: <0.000195% CI: [-0.585, -0.23]Mixed Models Analysis
Secondary
Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18
An absolute efficacy response is defined as HbA1c \< 6.5% at 18 weeks. A non-response is defined as HbA1c \>= 6.5% at 18 weeks.
Time frame: week 18
Population: FAS patients with baseline HbA1c \>= 6.5%. Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 | HbA1c < 6.5% | 2.4 percentage of participants |
| Placebo | Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 | HbA1c >= 6.5% | 97.6 percentage of participants |
| Linagliptin 5.0 mg | Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 | HbA1c < 6.5% | 5.7 percentage of participants |
| Linagliptin 5.0 mg | Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 | HbA1c >= 6.5% | 94.3 percentage of participants |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.243195% CI: [0.515, 13.652]Regression, Logistic
Secondary
Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18
An absolute efficacy response is defined as HbA1c \< 7.0% at 18 weeks. A non-response is defined as HbA1c \>= 7.0% at 18 weeks.
Time frame: week 18
Population: FAS patients with baseline HbA1c \>= 7.0%. Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 | HbA1c < 7% | 3.7 Percentage of Patients |
| Placebo | Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 | HbA1c >= 7% | 96.3 Percentage of Patients |
| Linagliptin 5.0 mg | Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 | HbA1c < 7% | 15.2 Percentage of Patients |
| Linagliptin 5.0 mg | Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 | HbA1c >= 7% | 84.8 Percentage of Patients |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.006595% CI: [1.684, 24.825]Regression, Logistic
Secondary
Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18
An efficacy response is defined as HbA1c lowered by 0.5% or more at 18 weeks. A non-response is defined as HbA1c not lowered by 0.5% or more at 18 weeks.
Time frame: Baseline, week 18
Population: FAS patients. Non-completers were considered as failure imputation (NCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 | HbA1c lower by at least 0.5% | 22 percentage of participants |
| Placebo | Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 | HbA1c not lower by at least 0.5% | 78.0 percentage of participants |
| Linagliptin 5.0 mg | Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 | HbA1c lower by at least 0.5% | 57.6 percentage of participants |
| Linagliptin 5.0 mg | Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 | HbA1c not lower by at least 0.5% | 42.4 percentage of participants |
Comparison: Linagliptin 5.0 mg versus placebop-value: 0.000195% CI: [2.747, 9.562]Regression, Logistic