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

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

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

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=5 Participants	53.1 years STANDARD_DEVIATION 9.7 • n=7 Participants	53.8 years STANDARD_DEVIATION 9.3 • n=5 Participants
Age, Customized < 65 years	79 participants n=5 Participants	162 participants n=7 Participants	241 participants n=5 Participants
Age, Customized 65 to 74 years	8 participants n=5 Participants	20 participants n=7 Participants	28 participants n=5 Participants
Age, Customized >= 75 years	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	100 Participants n=7 Participants	140 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	83 Participants n=7 Participants	132 Participants n=5 Participants
Weight	74.4 kilograms STANDARD_DEVIATION 19.8 • n=5 Participants	74.4 kilograms STANDARD_DEVIATION 20.4 • n=7 Participants	74.4 kilograms STANDARD_DEVIATION 20.2 • n=5 Participants
Weight categories <= 70 kilograms	46 participants n=5 Participants	97 participants n=7 Participants	143 participants n=5 Participants
Weight categories > 70 to 80 kilograms	17 participants n=5 Participants	32 participants n=7 Participants	49 participants n=5 Participants
Weight categories > 80 to 90 kilograms	10 participants n=5 Participants	18 participants n=7 Participants	28 participants n=5 Participants
Weight categories > 90 kilograms	16 participants n=5 Participants	36 participants n=7 Participants	52 participants n=5 Participants
Body Mass Index (BMI)	28.1 kilograms per square meter STANDARD_DEVIATION 5.5 • n=5 Participants	28.2 kilograms per square meter STANDARD_DEVIATION 5.2 • n=7 Participants	28.2 kilograms per square meter STANDARD_DEVIATION 5.3 • n=5 Participants
Body Mass Index (BMI) categories < 25 kilograms/square meter	29 participants n=5 Participants	51 participants n=7 Participants	80 participants n=5 Participants
Body Mass Index (BMI) categories >= 25 and < 30 kilograms/square meter	38 participants n=5 Participants	76 participants n=7 Participants	114 participants n=5 Participants
Body Mass Index (BMI) categories >= 30 kilograms/square meter	22 participants n=5 Participants	56 participants n=7 Participants	78 participants n=5 Participants
Height	162.0 centimeters STANDARD_DEVIATION 11.0 • n=5 Participants	161.4 centimeters STANDARD_DEVIATION 11.4 • n=7 Participants	161.6 centimeters STANDARD_DEVIATION 11.2 • n=5 Participants
Waist circumference	97.7 centimeters STANDARD_DEVIATION 13.5 • n=5 Participants	98.1 centimeters STANDARD_DEVIATION 13.1 • n=7 Participants	98.0 centimeters STANDARD_DEVIATION 13.2 • n=5 Participants
Smoking status Never smoked	75 participants n=5 Participants	151 participants n=7 Participants	226 participants n=5 Participants
Smoking status Ex-smoker	12 participants n=5 Participants	16 participants n=7 Participants	28 participants n=5 Participants
Smoking status Currently smokes	2 participants n=5 Participants	16 participants n=7 Participants	18 participants n=5 Participants
Alcohol status Non drinker	79 participants n=5 Participants	156 participants n=7 Participants	235 participants n=5 Participants
Alcohol status Drinks - no interference with study	10 participants n=5 Participants	27 participants n=7 Participants	37 participants n=5 Participants
Alcohol status Drinks - investigator opinion/interfere with study	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 24 weeks

Population: 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

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 weeks

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin

Outcome measures

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 weeks

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin

Outcome measures

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 weeks

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin

Outcome measures

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 weeks

Population: 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

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 weeks

Population: 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

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 weeks

Population: 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

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 weeks

Population: 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

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 weeks

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 6

Outcome measures

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 weeks

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 12

Outcome measures

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 weeks

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 18

Outcome measures

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

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

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