Trial Outcomes & Findings for Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes (NCT NCT00601250)
NCT ID: NCT00601250
Last Updated: 2014-01-28
Results Overview
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.
COMPLETED
PHASE3
701 participants
Baseline and week 24
2014-01-28
Participant Flow
Participant milestones
| Measure |
Placebo
Patients randomized to receive treatment with matching placebo
|
Linagliptin
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Overall Study
STARTED
|
177
|
523
|
|
Overall Study
COMPLETED
|
163
|
484
|
|
Overall Study
NOT COMPLETED
|
14
|
39
|
Reasons for withdrawal
| Measure |
Placebo
Patients randomized to receive treatment with matching placebo
|
Linagliptin
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
9
|
|
Overall Study
Protocol Violation
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
6
|
|
Overall Study
Withdrawal by Subject
|
4
|
13
|
|
Overall Study
Other incl. lack of efficacy
|
2
|
9
|
Baseline Characteristics
Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Placebo
n=177 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=523 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
Total
n=700 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.6 Years
STANDARD_DEVIATION 10.9 • n=93 Participants
|
56.5 Years
STANDARD_DEVIATION 10.1 • n=4 Participants
|
56.5 Years
STANDARD_DEVIATION 10.3 • n=27 Participants
|
|
Sex: Female, Male
Female
|
76 Participants
n=93 Participants
|
245 Participants
n=4 Participants
|
321 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=93 Participants
|
278 Participants
n=4 Participants
|
379 Participants
n=27 Participants
|
|
Body Mass Index (BMI) continuous
|
30.05 kg/m^2
STANDARD_DEVIATION 5.01 • n=93 Participants
|
29.85 kg/m^2
STANDARD_DEVIATION 4.84 • n=4 Participants
|
29.90 kg/m^2
STANDARD_DEVIATION 4.88 • n=27 Participants
|
|
Glycosylated haemoglobin A1 (HbA1C)
|
8.02 Percent
STANDARD_DEVIATION 0.88 • n=93 Participants
|
8.09 Percent
STANDARD_DEVIATION 0.86 • n=4 Participants
|
8.08 Percent
STANDARD_DEVIATION 0.87 • n=27 Participants
|
|
Fasting blood plasma glucose (FPG)
|
166.42 mg/dL
STANDARD_DEVIATION 41.89 • n=93 Participants
|
169.62 mg/dL
STANDARD_DEVIATION 43.51 • n=4 Participants
|
168.81 mg/dL
STANDARD_DEVIATION 43.10 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
HbA1c Change From Baseline at Week 24
|
0.15 Percent
Standard Error 0.06
|
-0.49 Percent
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline and week 6Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
HbA1c Change From Baseline at Week 6
|
0.069 Percent
Standard Error 0.044
|
-0.363 Percent
Standard Error 0.027
|
SECONDARY outcome
Timeframe: Baseline and week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
HbA1c Change From Baseline at Week 12
|
0.096 Percent
Standard Error 0.056
|
-0.499 Percent
Standard Error 0.034
|
SECONDARY outcome
Timeframe: Baseline and week 18Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
HbA1c Change From Baseline at Week 18
|
0.147 Percent
Standard Error 0.061
|
-0.502 Percent
Standard Error 0.037
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
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.
Outcome measures
| Measure |
Placebo
n=159 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=495 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
FPG Change From Baseline at Week 24
|
10.46 mg/dL
Standard Error 2.80
|
-10.68 mg/dL
Standard Error 1.65
|
SECONDARY outcome
Timeframe: Baseline and week 6Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
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.
Outcome measures
| Measure |
Placebo
n=159 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=495 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
FPG Change From Baseline at Week 6
|
4.58 mg/dL
Standard Error 2.38
|
-11.94 mg/dL
Standard Error 1.40
|
SECONDARY outcome
Timeframe: Baseline and week 12Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
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.
Outcome measures
| Measure |
Placebo
n=159 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=495 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
FPG Change From Baseline at Week 12
|
3.86 mg/dL
Standard Error 2.60
|
-12.86 mg/dL
Standard Error 1.52
|
SECONDARY outcome
Timeframe: Baseline and week 18Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.
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.
Outcome measures
| Measure |
Placebo
n=159 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=495 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
FPG Change From Baseline at Week 18
|
10.32 mg/dL
Standard Error 2.72
|
-10.51 mg/dL
Standard Error 1.60
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: This population includes the FAS with baseline HbA1c \>= 7.0%. Non-completers were considered as failure imputation (NCF).
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%
Outcome measures
| Measure |
Placebo
n=163 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=485 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Percentage of Patients With HbA1c <7.0% at Week 24.
|
9.2 percentage of patients
0.00
|
26.2 percentage of patients
0.00
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).
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%.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Percentage of Patients With HbA1c < 7.0% at Week 24
|
11.4 percentage of patients
|
28.3 percentage of patients
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: This population includes the FAS with baseline HbA1c \>= 6.5%. Non-completers were considered as failure imputation (NCF).
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%
Outcome measures
| Measure |
Placebo
n=171 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=511 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Percentage of Patients With HbA1c <6.5% at Week 24
|
2.3 percentage of patients
0.00
|
10.4 percentage of patients
0.00
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).
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%.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Percentage of Patients With HbA1c<6.5% at Week 24
|
3.4 percentage of patients
|
10.7 percentage of patients
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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).
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%.
Outcome measures
| Measure |
Placebo
n=175 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=513 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24
|
21.7 percentage of patients
0.00
|
49.7 percentage of patients
0.00
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: Meal Tolerance Test (MTT) set (treated and randomised patients with adequate MTT results available at the beginning and end of the randomised treatment period)
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.
Outcome measures
| Measure |
Placebo
n=21 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=78 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24
|
18.27 mg/dL
Standard Error 12.85
|
-48.86 mg/dL
Standard Error 7.35
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: Meal Tolerance Test (MTT) set (treated and randomised patients with adequate MTT results available at the beginning and end of the randomised treatment period)
This change from baseline reflects the Week 24 (2h PPG - FPG) minus the baseline (2h PPG - FPG). Means are treatment adjusted for baseline HbA1c, baseline 2h PPG increment over FPG and previous anti-diabetic medication.
Outcome measures
| Measure |
Placebo
n=21 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=74 Participants
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
2 Hour Post-Prandial Glucose (PPG) Increment Over Fasting Plasma Glucose (FPG) at Week 24
|
10.90 mg/dL
Standard Error 9.23
|
-30.90 mg/dL
Standard Error 5.62
|
Adverse Events
Placebo
Linagliptin
Serious adverse events
| Measure |
Placebo
n=177 participants at risk
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=523 participants at risk
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Infections and infestations
Blebitis
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Infections and infestations
Hepatitis viral
|
0.56%
1/177 • From day of first dose until 7 days after last dose
|
0.00%
0/523 • From day of first dose until 7 days after last dose
|
|
Injury, poisoning and procedural complications
Avulsion fracture
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Injury, poisoning and procedural complications
Snake bite
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.56%
1/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Nervous system disorders
Cerebral ischaemia
|
0.56%
1/177 • From day of first dose until 7 days after last dose
|
0.00%
0/523 • From day of first dose until 7 days after last dose
|
|
Nervous system disorders
Headache
|
0.56%
1/177 • From day of first dose until 7 days after last dose
|
0.00%
0/523 • From day of first dose until 7 days after last dose
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.38%
2/523 • From day of first dose until 7 days after last dose
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.38%
2/523 • From day of first dose until 7 days after last dose
|
|
Renal and urinary disorders
Renal mass
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Reproductive system and breast disorders
Rectocele
|
0.56%
1/177 • From day of first dose until 7 days after last dose
|
0.00%
0/523 • From day of first dose until 7 days after last dose
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
|
Vascular disorders
Hypertension
|
0.00%
0/177 • From day of first dose until 7 days after last dose
|
0.19%
1/523 • From day of first dose until 7 days after last dose
|
Other adverse events
| Measure |
Placebo
n=177 participants at risk
Patients randomized to receive treatment with matching placebo
|
Linagliptin
n=523 participants at risk
Patients randomized to receive treatment with Linagliptin 5 mg
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.1%
9/177 • From day of first dose until 7 days after last dose
|
5.2%
27/523 • From day of first dose until 7 days after last dose
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
14.7%
26/177 • From day of first dose until 7 days after last dose
|
5.2%
27/523 • From day of first dose until 7 days after last dose
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER