Trial Outcomes & Findings for Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks, in Drug naïve or Previously Treated Type 2 Diabetic Patients With Insufficient Glycaemic Control (NCT NCT01214239)

NCT ID: NCT01214239

Last Updated: 2016-08-25

Results Overview

Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 300 participants
• Primary outcome timeframe: Baseline and at week 24
• Results posted on: 2016-08-25

Participant Flow

A total of 608 patients were screened in 19 centres in China, Malaysia,and Philippines.A total of 300 patients were randomised in a 1:2 ratio to receive either placebo (99 patients) or linagliptin 5 mg (201 patients).

Six week (4 weeks of wash-out period, followed by by a two week open-label placebo run-in period) for patients pre-treated with one oral antidiabetic agent in addition to metformin or two weeks placebo run-in for patients pre-treated with metformin monotherapy

Participant milestones

Measure	Placebo Placebo	Linagliptin 5mg Linagliptin 5mg, once daily tablets, oral
Overall Study STARTED	99	200
Overall Study COMPLETED	87	182
Overall Study NOT COMPLETED	12	18

Reasons for withdrawal

Measure	Placebo Placebo	Linagliptin 5mg Linagliptin 5mg, once daily tablets, oral
Overall Study Adverse Event	3	4
Overall Study Protocol Violation	2	1
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	4	9
Overall Study Lack of Efficacy	1	2
Overall Study patient's private reason	1	1

Baseline Characteristics

Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks, in Drug naïve or Previously Treated Type 2 Diabetic Patients With Insufficient Glycaemic Control

Baseline characteristics by cohort

Measure	Placebo n=99 Participants Placebo	Linagliptin 5mg n=200 Participants Linagliptin 5mg, once daily tablets, oral	Total n=299 Participants Total of all reporting groups
Age, Continuous	54.1 years STANDARD_DEVIATION 9.3 • n=5 Participants	54.6 years STANDARD_DEVIATION 10.1 • n=7 Participants	54.4 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	84 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	116 Participants n=7 Participants	175 Participants n=5 Participants
BMI	25.1 kg/m2 STANDARD_DEVIATION 3.4 • n=5 Participants	25.5 kg/m2 STANDARD_DEVIATION 3.3 • n=7 Participants	25.4 kg/m2 STANDARD_DEVIATION 3.4 • n=5 Participants
Baseline HbA1c	8.09 % STANDARD_DEVIATION 0.91 • n=5 Participants	7.95 % STANDARD_DEVIATION 0.89 • n=7 Participants	7.99 % STANDARD_DEVIATION 0.90 • n=5 Participants
Baseline fasting plasma glucose	161.4 mg/dL STANDARD_DEVIATION 39.9 • n=5 Participants	151.4 mg/dL STANDARD_DEVIATION 32.4 • n=7 Participants	154.6 mg/dL STANDARD_DEVIATION 35.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 24	-0.18 % of HbA1c Standard Error 0.10	-0.68 % of HbA1c Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 6	-0.072 % of HbA1c Standard Error 0.065	-0.454 % of HbA1c Standard Error 0.049

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 12	-0.108 % of HbA1c Standard Error 0.08	-0.609 % of HbA1c Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 18	-0.159 % of HbA1c Standard Error 0.087	-0.670 % of HbA1c Standard Error 0.066

SECONDARY outcome

Timeframe: Baseline and at 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 (in the subset of Chinese patients). Last observation carried forward (LOCF) was used as the imputation rule.

Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=83 Participants Placebo	Linagliptin 5mg n=168 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 24 in the Subset of Chinese Patients	-0.23 % of HbA1c Standard Error 0.11	-0.69 % of HbA1c Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline fasting plasma glucose (FPG) and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 6	-0.8 mg/dL Standard Error 2.7	-12.0 mg/dL Standard Error 2.0

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 12	-2.1 mg/dL Standard Error 3.0	-11.0 mg/dL Standard Error 2.2

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 18	-1.0 mg/dL Standard Error 3.4	-10.5 mg/dL Standard Error 2.5

SECONDARY outcome

Timeframe: Baseline and at 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.

Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 24	1.5 mg/dL Standard Error 3.4	-8.1 mg/dL Standard Error 2.5

SECONDARY outcome

Timeframe: baseline and at 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. Non-completers were considered as failure imputation (NCF).

Number of patients with HbA1c < 7.0% at week 24

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 7.0%	26 Patients	94 Patients

SECONDARY outcome

Timeframe: baseline and at week 24

Population: This population includes the FAS with baseline HbA1c \>= 7.0%. Non-completers were considered as failure imputation (NCF).

Number of patients with HbA1c < 7.0% at week 24 with baseline HbA1c >= 7.0%.

Outcome measures

Measure	Placebo n=89 Participants Placebo	Linagliptin 5mg n=176 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%.	23 Patients	80 Patients

SECONDARY outcome

Timeframe: baseline and at 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. Non-completers were considered as failure imputation (NCF).

Number of patients with HbA1c < 6.5% at week 24

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 6.5%	12 Patients	38 Patients

SECONDARY outcome

Timeframe: baseline and at week 24

Population: This population includes the FAS with baseline HbA1c \>= 6.5%. Non-completers were considered as failure imputation (NCF).

Number of patients with HbA1c < 6.5% at week 24 with baseline HbA1c >= 6.5%.

Outcome measures

Measure	Placebo n=93 Participants Placebo	Linagliptin 5mg n=192 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%.	11 Patients	36 Patients

SECONDARY outcome

Timeframe: baseline and at 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. Non-completers were considered as failure imputation (NCF).

Number with HbA1c at least 0.5% lowering from baseline at week 24

Outcome measures

Measure	Placebo n=94 Participants Placebo	Linagliptin 5mg n=196 Participants Linagliptin 5mg, once daily tablets, oral
Number With HbA1c at Least Lowering 0.5%	43 Patients	128 Patients

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Linagliptin 5mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=99 participants at risk Placebo	Linagliptin 5mg n=200 participants at risk Linagliptin 5mg, once daily tablets, oral
Cardiac disorders Acute coronary syndrome	1.0% 1/99 • 24 weeks	0.00% 0/200 • 24 weeks
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.0% 1/99 • 24 weeks	0.00% 0/200 • 24 weeks
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.0% 1/99 • 24 weeks	0.00% 0/200 • 24 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/99 • 24 weeks	0.50% 1/200 • 24 weeks
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/99 • 24 weeks	0.50% 1/200 • 24 weeks

Other adverse events

Measure	Placebo n=99 participants at risk Placebo	Linagliptin 5mg n=200 participants at risk Linagliptin 5mg, once daily tablets, oral
Metabolism and nutrition disorders Hyperlipidaemia	3.0% 3/99 • 24 weeks	5.5% 11/200 • 24 weeks
Metabolism and nutrition disorders Hyperglycaemia	4.0% 4/99 • 24 weeks	2.0% 4/200 • 24 weeks

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
• Publication restrictions are in place