Trial Outcomes & Findings for Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy (NCT NCT01215097)

NCT ID: NCT01215097

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: 306 participants
• Primary outcome timeframe: Baseline and at week 24
• Results posted on: 2016-08-25

Participant Flow

A total of 614 patients were screened in 19 centres in China, Malaysia,and Philippines.A total of 306 patients were randomised in a 1:2 ratio to receive either placebo (101 patients) or linagliptin 5 mg (205 patients) in addition to metformin.

Participant milestones

Measure	Placebo Placebo	Linagliptin 5mg Linagliptin 5mg, once daily tablets, oral
Overall Study STARTED	100	205
Overall Study COMPLETED	88	191
Overall Study NOT COMPLETED	12	14

Reasons for withdrawal

Measure	Placebo Placebo	Linagliptin 5mg Linagliptin 5mg, once daily tablets, oral
Overall Study Adverse Event	1	3
Overall Study Protocol Violation	0	2
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	6	3
Overall Study Lack of Efficacy	0	3
Overall Study patient's refusal to come	2	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 Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

Baseline characteristics by cohort

Measure	Placebo n=100 Participants Placebo	Linagliptin 5mg n=205 Participants Linagliptin 5mg, once daily tablets, oral	Total n=305 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 8.7 • n=5 Participants	55.1 years STANDARD_DEVIATION 10.7 • n=7 Participants	55.5 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	103 Participants n=7 Participants	153 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	102 Participants n=7 Participants	152 Participants n=5 Participants
BMI	25.8 kg/m^2 STANDARD_DEVIATION 4.0 • n=5 Participants	25.5 kg/m^2 STANDARD_DEVIATION 3.9 • n=7 Participants	25.6 kg/m^2 STANDARD_DEVIATION 4.0 • n=5 Participants
Baseline HbA1c	8.00 % STANDARD_DEVIATION 0.80 • n=5 Participants	7.99 % STANDARD_DEVIATION 0.83 • n=7 Participants	7.99 % STANDARD_DEVIATION 0.82 • n=5 Participants
Baseline fasting plasma glucose	157.7 mg/dL STANDARD_DEVIATION 36.8 • n=5 Participants	160.5 mg/dL STANDARD_DEVIATION 40.1 • n=7 Participants	159.6 mg/dL STANDARD_DEVIATION 39.0 • 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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 24	-0.14 Percent Standard Error 0.07	-0.66 Percent Standard Error 0.05

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 6	-0.02 Percent Standard Error 0.052	-0.455 Percent Standard Error 0.037

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 12	-0.062 Percent Standard Error 0.068	-0.653 Percent Standard Error 0.048

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 18	-0.119 Percent Standard Error 0.073	-0.645 Percent Standard Error 0.052

SECONDARY outcome

Timeframe: Baseline and at 24 weeks

Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available (Chinese only). 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=77 Participants Placebo	Linagliptin 5mg n=182 Participants Linagliptin 5mg, once daily tablets, oral
HbA1c Change From Baseline at Week 24(Chinese Only)	-0.16 Percent Standard Error 0.08	-0.68 Percent Standard Error 0.06

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 fasting plasma glucose (FPG) and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 24	-1.1 mg/dL Standard Error 3.5	-10.7 mg/dL Standard Error 2.5

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 FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 6	5.3 mg/dL Standard Error 2.8	-16.8 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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 12	-4.5 mg/dL Standard Error 3.0	-14.7 mg/dL Standard Error 2.1

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
FPG Change From Baseline at Week 18	-1.9 mg/dL Standard Error 3.4	-13.4 mg/dL Standard Error 2.4

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 7.0%	14 Participants	82 Participants

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=185 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%.	9 Participants	69 Participants

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 6.5%	4 Participants	26 Participants

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=96 Participants Placebo	Linagliptin 5mg n=202 Participants Linagliptin 5mg, once daily tablets, oral
Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%.	3 Participants	26 Participants

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=97 Participants Placebo	Linagliptin 5mg n=203 Participants Linagliptin 5mg, once daily tablets, oral
Number With HbA1c at Least Lowering 0.5%	33 Participants	120 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Linagliptin 5mg

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=100 participants at risk Placebo	Linagliptin 5mg n=205 participants at risk Linagliptin 5mg, once daily tablets, oral
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/100 • 24 weeks	0.49% 1/205 • 24 weeks
Nervous system disorders Lacunar infarction	1.0% 1/100 • 24 weeks	0.00% 0/205 • 24 weeks
Hepatobiliary disorders Cholecystitis	1.0% 1/100 • 24 weeks	0.00% 0/205 • 24 weeks
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/100 • 24 weeks	0.49% 1/205 • 24 weeks
Investigations Alanine aminotransferase increased	0.00% 0/100 • 24 weeks	0.49% 1/205 • 24 weeks
Injury, poisoning and procedural complications Comminuted fracture	0.00% 0/100 • 24 weeks	0.49% 1/205 • 24 weeks

Other adverse events

Measure	Placebo n=100 participants at risk Placebo	Linagliptin 5mg n=205 participants at risk Linagliptin 5mg, once daily tablets, oral
Infections and infestations Upper respiratory tract infection	3.0% 3/100 • 24 weeks	1.5% 3/205 • 24 weeks
Infections and infestations Nasopharyngitis	1.0% 1/100 • 24 weeks	2.4% 5/205 • 24 weeks
Metabolism and nutrition disorders Hyperlipidaemia	4.0% 4/100 • 24 weeks	4.4% 9/205 • 24 weeks
Metabolism and nutrition disorders Hyperglycaemia	5.0% 5/100 • 24 weeks	4.9% 10/205 • 24 weeks
Gastrointestinal disorders Diarrhoea	1.0% 1/100 • 24 weeks	2.4% 5/205 • 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