Trial Outcomes & Findings for Efficacy and Safety of 3 Doses of BI1356 (Linagliptin) in Type 2 Diabetes Patients (NCT NCT00328172)
NCT ID: NCT00328172
Last Updated: 2014-03-14
Results Overview
The change from baseline reflects the Week 12 HbA1c minus the Week 0 HbA1c. Means are adjusted for baseline HbA1c.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
302 participants
Primary outcome timeframe
Baseline, week 12
Results posted on
2014-03-14
Participant Flow
Participant milestones
| Measure |
Placebo
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
67
|
58
|
57
|
55
|
65
|
|
Overall Study
COMPLETED
|
45
|
44
|
47
|
42
|
60
|
|
Overall Study
NOT COMPLETED
|
22
|
14
|
10
|
13
|
5
|
Reasons for withdrawal
| Measure |
Placebo
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
2
|
1
|
2
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
2
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
1
|
6
|
0
|
|
Overall Study
Lack of Efficacy
|
14
|
9
|
4
|
4
|
3
|
|
Overall Study
Other reason (not specified)
|
3
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Efficacy and Safety of 3 Doses of BI1356 (Linagliptin) in Type 2 Diabetes Patients
Baseline characteristics by cohort
| Measure |
Placebo
n=67 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
n=58 Participants
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
n=57 Participants
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
n=55 Participants
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
n=65 Participants
Patients randomized to receive treatment with metformin
|
Total
n=302 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
58.6 years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
58.0 years
STANDARD_DEVIATION 9.4 • n=7 Participants
|
59.8 years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
56.6 years
STANDARD_DEVIATION 9.6 • n=4 Participants
|
53.7 years
STANDARD_DEVIATION 10.7 • n=21 Participants
|
57.3 years
STANDARD_DEVIATION 9.9 • n=10 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
127 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
39 Participants
n=21 Participants
|
175 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic
|
63 participants
n=5 Participants
|
54 participants
n=7 Participants
|
51 participants
n=5 Participants
|
49 participants
n=4 Participants
|
61 participants
n=21 Participants
|
278 participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
6 participants
n=4 Participants
|
4 participants
n=21 Participants
|
24 participants
n=10 Participants
|
|
Race/Ethnicity, Customized
White
|
58 participants
n=5 Participants
|
52 participants
n=7 Participants
|
53 participants
n=5 Participants
|
52 participants
n=4 Participants
|
57 participants
n=21 Participants
|
272 participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Black
|
6 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
1 participants
n=4 Participants
|
5 participants
n=21 Participants
|
18 participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
2 participants
n=21 Participants
|
11 participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Missing
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
1 participants
n=10 Participants
|
|
Body Mass Index (BMI)
|
30.8 kilogram/square meter
STANDARD_DEVIATION 4.1 • n=5 Participants
|
30.9 kilogram/square meter
STANDARD_DEVIATION 3.8 • n=7 Participants
|
31.5 kilogram/square meter
STANDARD_DEVIATION 4.5 • n=5 Participants
|
31.2 kilogram/square meter
STANDARD_DEVIATION 4.3 • n=4 Participants
|
31.2 kilogram/square meter
STANDARD_DEVIATION 4.8 • n=21 Participants
|
31.1 kilogram/square meter
STANDARD_DEVIATION 4.3 • n=10 Participants
|
|
Baseline glycosylated hemoglobin (HbA1c)
|
8.3 percentage
STANDARD_DEVIATION 0.63 • n=5 Participants
|
8.2 percentage
STANDARD_DEVIATION 0.62 • n=7 Participants
|
8.4 percentage
STANDARD_DEVIATION 0.80 • n=5 Participants
|
8.4 percentage
STANDARD_DEVIATION 0.80 • n=4 Participants
|
8.3 percentage
STANDARD_DEVIATION 0.64 • n=21 Participants
|
8.3 percentage
STANDARD_DEVIATION 0.69 • n=10 Participants
|
|
Fasting blood plasma glucose (FPG)
|
183.0 milligram/deciliter (mg/dL)
STANDARD_DEVIATION 34.9 • n=5 Participants
|
185.2 milligram/deciliter (mg/dL)
STANDARD_DEVIATION 34.0 • n=7 Participants
|
191.9 milligram/deciliter (mg/dL)
STANDARD_DEVIATION 37.8 • n=5 Participants
|
188.7 milligram/deciliter (mg/dL)
STANDARD_DEVIATION 40.1 • n=4 Participants
|
193.9 milligram/deciliter (mg/dL)
STANDARD_DEVIATION 45.9 • n=21 Participants
|
188.4 milligram/deciliter (mg/dL)
STANDARD_DEVIATION 38.8 • n=10 Participants
|
PRIMARY outcome
Timeframe: Baseline, week 12Population: 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.
The change from baseline reflects the Week 12 HbA1c minus the Week 0 HbA1c. Means are adjusted for baseline HbA1c.
Outcome measures
| Measure |
Placebo
n=63 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
n=57 Participants
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
n=55 Participants
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
n=54 Participants
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
n=65 Participants
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 12
|
0.18 percent
Standard Error 0.10
|
0.04 percent
Standard Error 0.10
|
-0.24 percent
Standard Error 0.10
|
-0.28 percent
Standard Error 0.10
|
-0.68 percent
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Baseline, week 12Population: 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.
Change from baseline reflects the Week 12 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG.
Outcome measures
| Measure |
Placebo
n=63 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
n=57 Participants
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
n=55 Participants
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
n=54 Participants
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
n=65 Participants
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
|
4.24 mg/dL
Standard Error 4.4
|
6.69 mg/dL
Standard Error 4.6
|
-15.2 mg/dL
Standard Error 4.7
|
-9.09 mg/dL
Standard Error 4.8
|
-30.1 mg/dL
Standard Error 4.3
|
SECONDARY outcome
Timeframe: Baseline, week 12Population: FAS patients with baseline HbA1c \> 7.0%. Non-completers were considered as failure imputation (NCF).
An absolute efficacy response is defined as HbA1c \<= 7.0% at 12 weeks. A non-response is defined as HbA1c \> 7.0% at 12 weeks.
Outcome measures
| Measure |
Placebo
n=63 Participants
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
n=57 Participants
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
n=55 Participants
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
n=54 Participants
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
n=65 Participants
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Percentage of Patients With Absolute Efficacy Response (HbA1c <= 7.0%) at 12 Weeks
HbA1c <= 7%
|
6.3 participants
|
10.5 participants
|
7.3 participants
|
11.1 participants
|
26.2 participants
|
|
Percentage of Patients With Absolute Efficacy Response (HbA1c <= 7.0%) at 12 Weeks
HbA1c > 7%
|
93.7 participants
|
89.5 participants
|
92.7 participants
|
88.9 participants
|
73.8 participants
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Linagliptin (BI 1356) 0.5 mg
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Linagliptin (BI 1356) 2.5 mg
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Linagliptin (BI 1356) 5.0 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Metformin
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=67 participants at risk
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
n=58 participants at risk
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
n=57 participants at risk
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
n=55 participants at risk
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
n=65 participants at risk
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.7%
1/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Infections and infestations
Injection site abscess
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Infections and infestations
Obstructive chronic bronchitis with acute exacerbation
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Psychiatric disorders
Schizoaffective disorder
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.5%
1/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
1.5%
1/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
Other adverse events
| Measure |
Placebo
n=67 participants at risk
Patients randomized to receive treatment with matching placebo
|
Linagliptin (BI 1356) 0.5 mg
n=58 participants at risk
Patients randomized to receive treatment with linagliptin 0.5 mg
|
Linagliptin (BI 1356) 2.5 mg
n=57 participants at risk
Patients randomized to receive treatment with linagliptin 2.5 mg
|
Linagliptin (BI 1356) 5.0 mg
n=55 participants at risk
Patients randomized to receive treatment with linagliptin 5.0 mg
|
Metformin
n=65 participants at risk
Patients randomized to receive treatment with metformin
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.0%
2/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.4%
2/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
7.7%
5/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Infections and infestations
Influenza
|
1.5%
1/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.7%
1/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
5.3%
3/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Infections and infestations
Nasopharyngitis
|
7.5%
5/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.7%
1/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.5%
2/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.1%
2/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
5.2%
3/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Investigations
Blood glucose increased
|
6.0%
4/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.4%
2/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
0.00%
0/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.6%
2/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.1%
2/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.4%
7/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
12.1%
7/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.5%
2/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
4.6%
3/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
|
Nervous system disorders
Headache
|
1.5%
1/67 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
8.6%
5/58 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
1.8%
1/57 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
5.5%
3/55 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
3.1%
2/65 • First dose of study medication up to a period of 30 days after the last dose of study medication, an average of 106 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
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