Trial Outcomes & Findings for Linagliptin Versus Placebo in Type 2 Diabetic Patients With Inadequate Glycaemic Control on Metformin in Combination With Pioglitazone (NCT NCT00996658)
NCT ID: NCT00996658
Last Updated: 2014-03-26
Results Overview
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
278 participants
Primary outcome timeframe
baseline, 24 weeks
Results posted on
2014-03-26
Participant Flow
Participant milestones
| Measure |
Placebo Tablet
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Overall Study
STARTED
|
92
|
186
|
|
Overall Study
COMPLETED
|
76
|
165
|
|
Overall Study
NOT COMPLETED
|
16
|
21
|
Reasons for withdrawal
| Measure |
Placebo Tablet
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
5
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
5
|
|
Overall Study
Non-compliance issues
|
3
|
3
|
|
Overall Study
Other
|
9
|
7
|
Baseline Characteristics
Linagliptin Versus Placebo in Type 2 Diabetic Patients With Inadequate Glycaemic Control on Metformin in Combination With Pioglitazone
Baseline characteristics by cohort
| Measure |
Placebo Tablet
n=89 Participants
|
Linagliptin 5 mg Tablet
n=183 Participants
|
Total
n=272 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.2 years
STANDARD_DEVIATION 8.4 • n=99 Participants
|
53.1 years
STANDARD_DEVIATION 9.7 • n=107 Participants
|
53.8 years
STANDARD_DEVIATION 9.3 • n=206 Participants
|
|
Age, Customized
< 65 years
|
79 participants
n=99 Participants
|
162 participants
n=107 Participants
|
241 participants
n=206 Participants
|
|
Age, Customized
65 to 74 years
|
8 participants
n=99 Participants
|
20 participants
n=107 Participants
|
28 participants
n=206 Participants
|
|
Age, Customized
>= 75 years
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=99 Participants
|
100 Participants
n=107 Participants
|
140 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=99 Participants
|
83 Participants
n=107 Participants
|
132 Participants
n=206 Participants
|
|
Weight
|
74.4 kilograms
STANDARD_DEVIATION 19.8 • n=99 Participants
|
74.4 kilograms
STANDARD_DEVIATION 20.4 • n=107 Participants
|
74.4 kilograms
STANDARD_DEVIATION 20.2 • n=206 Participants
|
|
Weight categories
<= 70 kilograms
|
46 participants
n=99 Participants
|
97 participants
n=107 Participants
|
143 participants
n=206 Participants
|
|
Weight categories
> 70 to 80 kilograms
|
17 participants
n=99 Participants
|
32 participants
n=107 Participants
|
49 participants
n=206 Participants
|
|
Weight categories
> 80 to 90 kilograms
|
10 participants
n=99 Participants
|
18 participants
n=107 Participants
|
28 participants
n=206 Participants
|
|
Weight categories
> 90 kilograms
|
16 participants
n=99 Participants
|
36 participants
n=107 Participants
|
52 participants
n=206 Participants
|
|
Body Mass Index (BMI)
|
28.1 kilograms per square meter
STANDARD_DEVIATION 5.5 • n=99 Participants
|
28.2 kilograms per square meter
STANDARD_DEVIATION 5.2 • n=107 Participants
|
28.2 kilograms per square meter
STANDARD_DEVIATION 5.3 • n=206 Participants
|
|
Body Mass Index (BMI) categories
< 25 kilograms/square meter
|
29 participants
n=99 Participants
|
51 participants
n=107 Participants
|
80 participants
n=206 Participants
|
|
Body Mass Index (BMI) categories
>= 25 and < 30 kilograms/square meter
|
38 participants
n=99 Participants
|
76 participants
n=107 Participants
|
114 participants
n=206 Participants
|
|
Body Mass Index (BMI) categories
>= 30 kilograms/square meter
|
22 participants
n=99 Participants
|
56 participants
n=107 Participants
|
78 participants
n=206 Participants
|
|
Height
|
162.0 centimeters
STANDARD_DEVIATION 11.0 • n=99 Participants
|
161.4 centimeters
STANDARD_DEVIATION 11.4 • n=107 Participants
|
161.6 centimeters
STANDARD_DEVIATION 11.2 • n=206 Participants
|
|
Waist circumference
|
97.7 centimeters
STANDARD_DEVIATION 13.5 • n=99 Participants
|
98.1 centimeters
STANDARD_DEVIATION 13.1 • n=107 Participants
|
98.0 centimeters
STANDARD_DEVIATION 13.2 • n=206 Participants
|
|
Smoking status
Never smoked
|
75 participants
n=99 Participants
|
151 participants
n=107 Participants
|
226 participants
n=206 Participants
|
|
Smoking status
Ex-smoker
|
12 participants
n=99 Participants
|
16 participants
n=107 Participants
|
28 participants
n=206 Participants
|
|
Smoking status
Currently smokes
|
2 participants
n=99 Participants
|
16 participants
n=107 Participants
|
18 participants
n=206 Participants
|
|
Alcohol status
Non drinker
|
79 participants
n=99 Participants
|
156 participants
n=107 Participants
|
235 participants
n=206 Participants
|
|
Alcohol status
Drinks - no interference with study
|
10 participants
n=99 Participants
|
27 participants
n=107 Participants
|
37 participants
n=206 Participants
|
|
Alcohol status
Drinks - investigator opinion/interfere with study
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: baseline, 24 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=89 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=179 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks
|
-0.27 Percentage
Standard Error 0.13
|
-0.84 Percentage
Standard Error 0.11
|
SECONDARY outcome
Timeframe: baseline, 6 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=89 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=179 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks
|
-0.19 Percentage
Standard Error 0.11
|
-0.60 Percentage
Standard Error 0.09
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=89 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=179 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks
|
-0.28 Percentage
Standard Error 0.12
|
-0.82 Percentage
Standard Error 0.10
|
SECONDARY outcome
Timeframe: baseline, 18 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=89 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=179 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks
|
-0.37 Percentage
Standard Error 0.12
|
-0.91 Percentage
Standard Error 0.10
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had HbA1c \>=7.0% at baseline (NCF). Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=87 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=176 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks
Responder (HbA1c < 7.0%)
|
12 Participants
|
57 Participants
|
|
Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks
Non-responder (HbA1c >= 7.0%)
|
75 Participants
|
118 Participants
|
|
Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks
Missing
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had HbA1c \>=6.5% at baseline (NCF). Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=89 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=178 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks
Responder (HbA1c < 6.5%)
|
5 Participants
|
34 Participants
|
|
Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks
Non-responder (HbA1c >= 6.5%)
|
84 Participants
|
143 Participants
|
|
Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks
Missing
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication. Three subjects in each arm excluded for site non-compliance.
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Outcome measures
| Measure |
Placebo Tablet
n=89 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=179 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks
Responder (reduction in HbA1c >= 0.5%)
|
44 Participants
|
117 Participants
|
|
Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks
Non-responder (reduction in HbA1c < 0.5%)
|
45 Participants
|
61 Participants
|
|
Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks
Missing
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: baseline, 24 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline FPG value and an on-treatment FPG value. Three subjects in each arm excluded for site non-compliance.
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 24
Outcome measures
| Measure |
Placebo Tablet
n=86 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=175 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks
|
0.1 mg/dL (milligrams per deciliter)
Standard Error 3.8
|
-10.3 mg/dL (milligrams per deciliter)
Standard Error 2.7
|
SECONDARY outcome
Timeframe: baseline, 6 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline FPG value and an on-treatment FPG value. Three subjects in each arm excluded for site non-compliance.
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 6
Outcome measures
| Measure |
Placebo Tablet
n=86 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=175 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) After 6 Weeks
|
12.4 mg/dL (milligrams per deciliter)
Standard Error 5.4
|
-3.3 mg/dL (milligrams per deciliter)
Standard Error 4.6
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline FPG value and an on-treatment FPG value. Three subjects in each arm excluded for site non-compliance.
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 12
Outcome measures
| Measure |
Placebo Tablet
n=86 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=175 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks
|
3.8 mg/dL (milligrams per deciliter)
Standard Error 4.6
|
-7.1 mg/dL (milligrams per deciliter)
Standard Error 3.6
|
SECONDARY outcome
Timeframe: baseline, 18 weeksPopulation: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline FPG value and an on-treatment FPG value. Three subjects in each arm excluded for site non-compliance.
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 18
Outcome measures
| Measure |
Placebo Tablet
n=86 Participants
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=175 Participants
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) After 18 Weeks
|
-2.4 mg/dL (milligrams per deciliter)
Standard Error 4.1
|
-8.6 mg/dL (milligrams per deciliter)
Standard Error 2.8
|
Adverse Events
Placebo Tablet
Serious events: 3 serious events
Other events: 16 other events
Deaths: 0 deaths
Linagliptin 5 mg Tablet
Serious events: 4 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Tablet
n=89 participants at risk
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=183 participants at risk
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.55%
1/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.1%
1/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.00%
0/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Eye disorders
Cataract
|
0.00%
0/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.55%
1/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.55%
1/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Infections and infestations
Hepatitis E
|
1.1%
1/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.00%
0/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.55%
1/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Renal and urinary disorders
Calculus bladder
|
0.00%
0/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.55%
1/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
1.1%
1/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
0.00%
0/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
Other adverse events
| Measure |
Placebo Tablet
n=89 participants at risk
Placebo matching linagliptin 5 mg tablet
|
Linagliptin 5 mg Tablet
n=183 participants at risk
Linagliptin 5 mg (milligrams) tablet given by mouth once daily
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.7%
6/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
7.1%
13/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.9%
7/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
6.0%
11/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
4.5%
4/89 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
5.5%
10/183 • From drug start up to drug stop (max 24 weeks)+ 7 days
For the analysis of AEs, all events with an onset after the first dose of trial medication up to a period of 7 days after the last dose of trial medication were assigned to the randomised treatment period.
|
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