Trial Outcomes & Findings for Efficacy and Safety of BI 1356 (Linagliptin) Versus Placebo in Type 2 Diabetic Patients With Insufficient Glycemic Control (NCT NCT00621140)

NCT ID: NCT00621140

Last Updated: 2014-02-17

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 503 participants
• Primary outcome timeframe: Baseline and week 24
• Results posted on: 2014-02-17

Participant Flow

Participant milestones

Measure	Placebo Patients randomized to receive treatment with matching placebo	Linagliptin Patients randomized to receive treatment with Linagliptin 5mg
Overall Study STARTED	167	336
Overall Study COMPLETED	152	318
Overall Study NOT COMPLETED	15	18

Reasons for withdrawal

Measure	Placebo Patients randomized to receive treatment with matching placebo	Linagliptin Patients randomized to receive treatment with Linagliptin 5mg
Overall Study Adverse Event	4	5
Overall Study Lost to Follow-up	1	2
Overall Study Withdrawal by Subject	4	6
Overall Study Other incl. lack of efficacy	6	5

Baseline Characteristics

Efficacy and Safety of BI 1356 (Linagliptin) Versus Placebo in Type 2 Diabetic Patients With Insufficient Glycemic Control

Baseline characteristics by cohort

Measure	Placebo n=167 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=336 Participants Patients randomized to receive treatment with Linagliptin 5mg	Total n=503 Participants Total of all reporting groups
Age, Continuous	54.4 Years STANDARD_DEVIATION 10.3 • n=5 Participants	56.4 Years STANDARD_DEVIATION 10.1 • n=7 Participants	55.7 Years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	172 Participants n=7 Participants	260 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	164 Participants n=7 Participants	243 Participants n=5 Participants
Body Mass Index (BMI) continuous	29.08 kg/m^2 STANDARD_DEVIATION 4.84 • n=5 Participants	29.04 kg/m^2 STANDARD_DEVIATION 4.80 • n=7 Participants	29.05 kg/m^2 STANDARD_DEVIATION 4.81 • n=5 Participants
Glycosylated Hemoglobin A1 (HbA1C)	8.00 Percent STANDARD_DEVIATION 0.86 • n=5 Participants	8.00 Percent STANDARD_DEVIATION 0.87 • n=7 Participants	8.00 Percent STANDARD_DEVIATION 0.67 • n=5 Participants
Fasting plasma glucose (FPG)	168.7 mg/dL STANDARD_DEVIATION 39.3 • n=5 Participants	164.7 mg/dL STANDARD_DEVIATION 41.9 • n=7 Participants	166.0 mg/dL STANDARD_DEVIATION 41.1 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline at Week 24	0.25 Percent Standard Error 0.07	-0.44 Percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 6

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline at Week 6	0.09 Percent Standard Error 0.05	-0.37 Percent Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and week 12

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline at Week 12	0.16 Percent Standard Error 0.06	-0.46 Percent Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and week 18

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline at Week 18	0.21 Percent Standard Error 0.07	-0.45 Percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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=149 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=318 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline at Week 24	14.84 mg/dL Standard Error 2.98	-8.47 mg/dL Standard Error 2.03

SECONDARY outcome

Timeframe: Baseline and week 6

Population: 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=149 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=318 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline at Week 6	6.73 mg/dL Standard Error 2.33	-10.87 mg/dL Standard Error 1.59

SECONDARY outcome

Timeframe: Baseline and week 12

Population: 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=149 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=318 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline at Week 12	10.23 mg/dL Standard Error 2.63	-10.75 mg/dL Standard Error 1.80

SECONDARY outcome

Timeframe: Baseline and week 18

Population: 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=149 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=318 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline at Week 18	13.11 mg/dL Standard Error 2.82	-7.25 mg/dL Standard Error 1.93

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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=147 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=306 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c <7.0% at Week 24	11.6 percentage of patients 0	25.2 percentage of patients 0

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c<7.0% at Week 24	15.3 percentage of patients	28.2 percentage of patients

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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=162 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=329 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c <6.5% at Week 24	4.9 percentage of patients 0	10.6 percentage of patients 0

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c<6.5% at Week 24	4.9 Percentage of Patients	10.8 Percentage of Patients

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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=163 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=333 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c Lowering by 0.5% at Week 24	19.0 percentage of patients 0	47.1 percentage of patients 0

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Meal Tolerance Test (MTT) set (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=24 Participants Patients randomized to receive treatment with matching placebo	Linagliptin n=67 Participants Patients randomized to receive treatment with Linagliptin 5mg
Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24	24.87 mg/dL Standard Error 10.33	-33.51 mg/dL Standard Error 6.19

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 38 other events

Deaths: 0 deaths

Linagliptin

Serious events: 10 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=167 participants at risk Patients randomized to receive treatment with matching placebo	Linagliptin n=336 participants at risk Patients randomized to receive treatment with Linagliptin 5mg
Cardiac disorders Atrial fibrillation	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Cardiac disorders Coronary artery disease	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Infections and infestations Cellulitis pharyngeal	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Infections and infestations Pneumonia	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Injury, poisoning and procedural complications Foot fracture	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.00% 0/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Injury, poisoning and procedural complications Hand fracture	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Injury, poisoning and procedural complications Rib fracture	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.00% 0/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Injury, poisoning and procedural complications Road traffic accident	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Investigations Platelet count decreased	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.00% 0/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.60% 1/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.00% 0/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.2% 2/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.00% 0/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Vascular disorders Hypertensive crisis	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Vascular disorders Hypotension	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days
Vascular disorders Temporal arteritis	0.00% 0/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	0.30% 1/336 • From day of first drug dose until 7 days after last dose, an average of 167 days

Other adverse events

Measure	Placebo n=167 participants at risk Patients randomized to receive treatment with matching placebo	Linagliptin n=336 participants at risk Patients randomized to receive treatment with Linagliptin 5mg
Metabolism and nutrition disorders Hyperglycaemia	22.8% 38/167 • From day of first drug dose until 7 days after last dose, an average of 167 days	8.6% 29/336 • From day of first drug dose until 7 days after last dose, an average of 167 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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