Japanese P III vs Voglibose and Placebo

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00654381
• Collaborator: (none)
• Enrollment: 561
• Locations: 47
• Arms: 4
• Patients Per Site: 11.9

Study Details

Study Description

Brief Summary

The objective of the current study is to investigate the efficacy, safety and tolerability of Linagliptin (BI 1356) (5 mg or 10 mg / once daily) compared to placebo given for 12 weeks and voglibose for 26 weeks as mono therapy in patients with type 2 diabetes mellitus with insufficient glycaemic control. Furthermore, long-term safety is evaluated with an extension treatment to 52 weeks.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: BI 1356; Drug: BI 1356; Drug: voglibose placebo; Drug: BI 1356 placebo; Drug: voglibose	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 561 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Double-blind Phase III Study to Evaluate the Efficacy of BI 1356 5 mg and 10 mg vs. Placebo for 12 Weeks and vs. Voglibose 0.6 mg for 26 Weeks in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control, Followed by an Extension Study to 52 Weeks to Evaluate Long-term Safety
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: voglibose 0.2 mg three times a day (TID) patient to receive a tablet containing 0.2 mg voglibose TID plus 2 placebo tablets matching BI 1356	Drug: voglibose; 0.6 mg/daily
Experimental: BI 1356 low dose patient to receive a tablet containing BI 1356 and matching placebo plus 3 placebo tablets matching voglibose	Drug: BI 1356; 5 mg/daily
Experimental: BI 1356 high dose patient to receive 2 tablets containing BI 1356 plus 3 placebo tablets matching voglibose	Drug: BI 1356; 10 mg/daily
Placebo Comparator: placebo patient to receive 2 placebo tablets matching BI 1356 plus 3 placebo tablets matching voglibose	Drug: voglibose placebo; three times daily; Drug: BI 1356 placebo; once daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c at Week 12 [12 weeks]

   Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication

2. Change From Baseline in HbA1c at Week 26 [26 weeks]

   Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication

3. Examination of Long-term Safety of Linagliptin (52-week Treatment) [52 weeks]

   The incidence of AEs (Preferred Terms) with a frequency of 5% or more in the patients with type 2 diabetes mellitus who received linagliptin (5 mg or 10 mg) once daily for 52 weeks

Secondary Outcome Measures

1. Relative Efficacy Response of HbA1c at Week 12 [12 weeks]

   HbA1c value decreased below 7.0%, below 6.5% and reduction from baseline ≥0.5% at Week 12

2. Relative Efficacy Response of HbA1c at Week 26 [26 weeks]

   HbA1c value decreased below 7.0%, below 6.5% and reduction from baseline ≥0.5% at Week 26

3. Relative Efficacy Response of HbA1c at Week 52 [52 weeks]

   HbA1c value decreased below 7.0%, below 6.5% and reduction from baseline ≥0.5% at Week 52

4. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 [12 weeks]

   Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication

5. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [26 weeks]

   Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication

6. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 [52 weeks]

   Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Japanese patients with a diagnosis of type 2 diabetes mellitus. Antidiabetic therapy has to be stable for at least 10 weeks before Visit 1.

2. Glycosylated haemoglobin A1 (HbA1c) 7.0 - 10.0% at Visit 3 (beginning of the 2-week placebo run-in phase)

3. Age: >= 20 and <= 80

4. Body Mass Index (BMI) <= 40 kg/m2

Exclusion criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months before Visit 1

2. Impaired hepatic function

3. History of severe allergy/hypersensitivity

4. Treatment with anti-diabetic, anti obesity drugs, etc 3 months before Visit 1

5. Fasting blood glucose >240 mg/dl (=13.3 mmol/L) at Visits 2 or 3

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1218.23.05 Boehringer Ingelheim Investigational Site	Asahi, Chiba		Japan
2	1218.23.06 Boehringer Ingelheim Investigational Site	Funabashi, Chiba		Japan
3	1218.23.21 Boehringer Ingelheim Investigational Site	Hitachinaka, Ibaraki		Japan
4	1218.23.44 Boehringer Ingelheim Investigational Site	Hitachiota, Ibaraki		Japan
5	1218.23.09 Boehringer Ingelheim Investigational Site	Imizu, Toyama		Japan
6	1218.23.45 Boehringer Ingelheim Investigational Site	Inashiki-gun, Ibaraki		Japan
7	1218.23.13 Boehringer Ingelheim Investigational Site	Izumisano, Osaka		Japan
8	1218.23.27 Boehringer Ingelheim Investigational Site	Kariya, Aichi		Japan
9	1218.23.47 Boehringer Ingelheim Investigational Site	Kitakatsushika-gun, Saitama		Japan
10	1218.23.39 Boehringer Ingelheim Investigational Site	Kitakyuushuu, Fukuoka		Japan
11	1218.23.02 Boehringer Ingelheim Investigational Site	Koriyama, Fukushima		Japan
12	1218.23.03 Boehringer Ingelheim Investigational Site	Koriyama, Fukushima		Japan
13	1218.23.10 Boehringer Ingelheim Investigational Site	Kyoto, Kyoto		Japan
14	1218.23.37 Boehringer Ingelheim Investigational Site	Marugame, Kagawa		Japan
15	1218.23.38 Boehringer Ingelheim Investigational Site	Marugame, Kagawa		Japan
16	1218.23.23 Boehringer Ingelheim Investigational Site	Matsumoto, Nagano		Japan
17	1218.23.07 Boehringer Ingelheim Investigational Site	Meguro-ku, Tokyo		Japan
18	1218.23.25 Boehringer Ingelheim Investigational Site	Nagoya, Aichi		Japan
19	1218.23.26 Boehringer Ingelheim Investigational Site	Nagoya, Aichi		Japan
20	1218.23.28 Boehringer Ingelheim Investigational Site	Nagoya, Aichi		Japan
21	1218.23.29 Boehringer Ingelheim Investigational Site	Nagoya, Aichi		Japan
22	1218.23.30 Boehringer Ingelheim Investigational Site	Nagoya, Aichi		Japan
23	1218.23.04 Boehringer Ingelheim Investigational Site	Naka, Ibaraki		Japan
24	1218.23.15 Boehringer Ingelheim Investigational Site	Nishi-ku, Hiroshima, Hiroshima		Japan
25	1218.23.34 Boehringer Ingelheim Investigational Site	Nishi-ku, Sakai, Osaka		Japan
26	1218.23.22 Boehringer Ingelheim Investigational Site	Nishishinjyuku, Shinjyuku-ku, Tokyo		Japan
27	1218.23.16 Boehringer Ingelheim Investigational Site	Oita, Oita		Japan
28	1218.23.40 Boehringer Ingelheim Investigational Site	Oita, Oita		Japan
29	1218.23.36 Boehringer Ingelheim Investigational Site	Okayama, Okayama		Japan
30	1218.23.11 Boehringer Ingelheim Investigational Site	Osaka, Osaka		Japan
31	1218.23.12 Boehringer Ingelheim Investigational Site	Osaka, Osaka		Japan
32	1218.23.32 Boehringer Ingelheim Investigational Site	Osaka, Osaka		Japan
33	1218.23.33 Boehringer Ingelheim Investigational Site	Osaka, Osaka		Japan
34	1218.23.35 Boehringer Ingelheim Investigational Site	Osaka, Osaka		Japan
35	1218.23.17 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido		Japan
36	1218.23.18 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido		Japan
37	1218.23.19 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido		Japan
38	1218.23.41 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido		Japan
39	1218.23.42 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido		Japan
40	1218.23.43 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido		Japan
41	1218.23.01 Boehringer Ingelheim Investigational Site	Sendai, Miyagi		Japan
42	1218.23.20 Boehringer Ingelheim Investigational Site	Sendai, Miyagi		Japan
43	1218.23.46 Boehringer Ingelheim Investigational Site	Shinjuku-ku, Tokyo		Japan
44	1218.23.08 Boehringer Ingelheim Investigational Site	Shinjyuku-ku,Tokyo		Japan
45	1218.23.14 Boehringer Ingelheim Investigational Site	Suita, Osaka		Japan
46	1218.23.31 Boehringer Ingelheim Investigational Site	Takatsuki, Osaka		Japan
47	1218.23.48 Boehringer Ingelheim Investigational Site	Yokohama, Kanagawa		Japan

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00654381
• Other Study ID Numbers: 1218.23
• First Posted: Apr 8, 2008
• Last Update Posted: Jan 27, 2014
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Inositol; Linagliptin; Voglibose

Study Results

Participant Flow

Recruitment Details	Total 6 groups (including sub-groups in placebo and voglibose groups)
Pre-assignment Detail	Placebo group has 2 sub-groups, placebo-linagliptin 5mg (from 2nd stage) and placebo-linagliptin 10mg (from 2nd stage). Both Linagliptin 5 mg and 10 mg groups don't have sub-group. Voglibose group has 2 sub-groups, voglibose-linagliptin 5mg (from 3rd stage) and voglibose-linagliptin 10mg (from 3rd stage).

Arm/Group Title	Placebo - BI1356 (Linagliptin) 5mg - Linagliptin 5mg	Placebo - Linagliptin 5mg - Linagliptin 10mg	Linagliptin 5mg - Linagliptin 5mg - Linagliptin 5mg	Linagliptin 10 mg - Linagliptin 10 mg - Linagliptin 10 mg	Voglibose - Voglibose - Linagliptin 5mg	Voglibose - Voglibose - Linagliptin 10mg
Arm/Group Description	Placebo in Stage 1 - 5 mg in Stage 2 - 5 mg in Stage 3	Placebo in Stage 1 - 10 mg in Stage 2 - 10 mg in Stage 3	5 mg in Stage 1 - 5 mg in Stage 2 - 5 mg in Stage 3	10 mg in Stage 1 - 10 mg in Stage 2 - 10 mg in Stage 3	Voglibose in Stage 1 - Voglibose in Stage 2 - 5 mg in Stage 3	Voglibose in Stage 1 - Voglibose in Stage 2 - 10 mg in Stage 3
Period Title: 1st Stage
STARTED	39	41	159	160	81	81
COMPLETED	36	38	156	155	79	79
NOT COMPLETED	3	3	3	5	2	2
Period Title: 1st Stage
STARTED	36	38	156	155	79	79
COMPLETED	34	38	153	151	71	76
NOT COMPLETED	2	0	3	4	8	3
Period Title: 1st Stage
STARTED	34	38	153	151	71	76
COMPLETED	33	36	142	142	68	73
NOT COMPLETED	1	2	11	9	3	3

Baseline Characteristics

Arm/Group Title	Placebo	Linagliptin 5mg	Linagliptin 10 mg	Voglibose	Total
Arm/Group Description	The patients with placebo at the start of randomised study medication	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication	The patients with voglibose at the start of randomised study medication	Total of all reporting groups
Overall Participants	80	159	160	162	561
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (8.9)	60.3 (9.4)	61.3 (10)	58.5 (9.9)	60.0 (9.7)
Sex: Female, Male (Count of Participants)
Female	23 28.8%	48 30.2%	48 30%	47 29%	166 29.6%
Male	57 71.3%	111 69.8%	112 70%	115 71%	395 70.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c at Week 12
Description	Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

For the 12-week analysis, it was planed the comparison between Linagliptin and placebo. Then the patients with voglibose were excluded in this analysis.Full analysis set for 12-week treatment period with Last Observation Carried Forward.

Arm/Group Title	Placebo	Linagliptin 5mg	Linagliptin 10 mg
Arm/Group Description	The patients with placebo at the start of randomised study medication	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication
Measure Participants	80	159	157
Least Squares Mean (Standard Error) [Percent]	0.63 (0.08)	-0.24 (0.06)	-0.25 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments	Linagliptin 5 mg vs placebo at week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline HbA1c, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 10 mg
	Comments	Linagliptin 10 mg vs placebo at week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline HbA1c, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95%; -1.05 to -0.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in HbA1c at Week 26
Description	Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

For the 26-week analysis, it was planed the comparison between Linagliptin and Voglibose. Then the patients with placebo were excluded in this analysis.Full analysis set for 26-week treatment period with Last Observation Carried Forward.

Arm/Group Title	Linagliptin 5mg	Linagliptin 10 mg	Voglibose
Arm/Group Description	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication	The patients with voglibose at the start of randomised study medication
Measure Participants	159	157	162
Least Squares Mean (Standard Error) [Percent]	-0.13 (0.07)	-0.19 (0.07)	0.19 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline HbA1c, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.49 to -0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Linagliptin 5mg, Linagliptin 10 mg
	Comments	Linagliptin 10 mg vs voglibose at week 26
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline HbA1c, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.56 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

3. Secondary Outcome

Title	Relative Efficacy Response of HbA1c at Week 12
Description	HbA1c value decreased below 7.0%, below 6.5% and reduction from baseline ≥0.5% at Week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

For the 12-week analysis, it was planed the comparison between Linagliptin and placebo. Then the patients with voglibose were excluded in this analysis.Full analysis set for 12-week treatment period with Last Observation Carried Forward.

Arm/Group Title	Placebo	Linagliptin 5mg	Linagliptin 10 mg
Arm/Group Description	The patients with placebo at the start of randomised study medication	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication
Measure Participants	80	159	157
HbA1c <7.0%	8 10%	42 26.4%	56 35%
HbA1c <6.5%	0 0%	15 9.4%	18 11.3%
HbA1c reduction from baseline ≥0.5%	7 8.8%	91 57.2%	94 58.8%

4. Secondary Outcome

Title	Relative Efficacy Response of HbA1c at Week 26
Description	HbA1c value decreased below 7.0%, below 6.5% and reduction from baseline ≥0.5% at Week 26
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

For the 26-week analysis, it was planed the comparison between Linagliptin and Voglibose. Then the patients with placebo were excluded in this analysis.Full analysis set for 26-week treatment period with Last Observation Carried Forward.

Arm/Group Title	Linagliptin 5mg	Linagliptin 10 mg	Voglibose
Arm/Group Description	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication	The patients with voglibose at the start of randomised study medication
Measure Participants	159	157	162
HbA1c <7.0%	48 60%	54 34%	36 22.5%
HbA1c <6.5%	15 18.8%	21 13.2%	7 4.4%
HbA1c reduction from baseline ≥0.5%	91 113.8%	84 52.8%	61 38.1%

5. Secondary Outcome

Title	Relative Efficacy Response of HbA1c at Week 52
Description	HbA1c value decreased below 7.0%, below 6.5% and reduction from baseline ≥0.5% at Week 52
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

For the 52-week analysis, it was planed to analyse for Linagliptin 5mg and 10mg. Then the patients with placebo and voglibose were excluded in this analysis. Full analysis set for 52-week treatment period with Last Observation Carried Forward

Arm/Group Title	Linagliptin 5mg	Linagliptin 10mg
Arm/Group Description	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication
Measure Participants	159	157
HbA1c <7.0%	38 47.5%	29 18.2%
HbA1c <6.5%	6 7.5%	10 6.3%
HbA1c reduction from baseline ≥0.5%	62 77.5%	62 39%

6. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Description	Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

For the 12-week analysis, it was planed the comparison between Linagliptin and placebo. Then the patients with voglibose were excluded in this analysis.Full analysis set for 12-week treatment period with Last Observation Carried Forward.

Arm/Group Title	Placebo	Linagliptin 5mg	Linagliptin 10 mg
Arm/Group Description	The patients with placebo at the start of randomised study medication	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication
Measure Participants	80	159	160
Least Squares Mean (Standard Error) [mg/dL]	7.4 (2.5)	-12.3 (1.9)	-13.0 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments	Linagliptin 5 mg vs placebo at week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline FPG, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-19.7
	Confidence Interval	(2-Sided) 95%; -25.4 to -14.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 10 mg
	Comments	Linagliptin 10 mg vs placebo at week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline FPG, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-20.4
	Confidence Interval	(2-Sided) 95%; -26.2 to -14.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Description	Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

For the 26-week analysis, it was planed the comparison between Linagliptin and Voglibose. Then the patients with placebo were excluded in this analysis.Full analysis set for 26-week treatment period with Last Observation Carried Forward

Arm/Group Title	Linagliptin 5mg	Linagliptin 10 mg	Voglibose
Arm/Group Description	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication	The patients with voglibose at the start of randomised study medication
Measure Participants	159	160	162
Least Squares Mean (Standard Error) [mg/dL]	-5.0 (2.4)	-7.8 (2.4)	2.0 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 10 mg
	Comments	Linagliptin 5 mg vs Voglibose at week 26
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0239
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline FPG, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-6.9
	Confidence Interval	(2-Sided) 95%; -13.0 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Linagliptin 5mg, Linagliptin 10 mg
	Comments	Linagliptin 10 mg vs voglibose at week 26
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	ANCOVA
	Comments	Model includes treatment,baseline FPG, and number of previous antidiabetic medication
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-9.8
	Confidence Interval	(2-Sided) 95%; -15.8 to -3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52
Description	Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The patients who had at least one available baseline FPG measurement under the treatment with linagliptin

Arm/Group Title	Linagliptin 5mg	Linagliptin 10 mg
Arm/Group Description	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication
Measure Participants	159	160
Least Squares Mean (Standard Error) [mg/dL]	-3.2 (2.7)	-5.9 (2.7)

9. Primary Outcome

Title	Examination of Long-term Safety of Linagliptin (52-week Treatment)
Description	The incidence of AEs (Preferred Terms) with a frequency of 5% or more in the patients with type 2 diabetes mellitus who received linagliptin (5 mg or 10 mg) once daily for 52 weeks
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The patients who received at least one dose of linagliptin 5 mg or linagliptin 10 mg during the randomised treatment period

Arm/Group Title	Linagliptin 5mg	Linagliptin 10 mg
Arm/Group Description	The patients with linagliptin 5 mg at the start of randomised study medication	The patients with linagliptin 10 mg at the start of randomised study medication
Measure Participants	266	274
Nasopharyngitis	84 105%	81 50.9%
Back pain	15 18.8%	21 13.2%
Constipation	12 15%	19 11.9%

Adverse Events

Time Frame	52 weeks
Arm/Group Title	Placebo (1st Stage)		Linagliptin 5mg (2nd-Extension Stage After Placebo)		Linagliptin 10mg (2nd-Extension Stage After Placebo)		Linagliptin 5mg (1st-2nd-Extension Stage)		Linagliptin 10mg (1st-2nd-Extension Stage)		Voglibose (1st-2nd Stage)		Linagliptin 5mg (Extension Stage After Voglibose)		Linagliptin 10mg (Extension Stage After Voglibose)
Arm/Group Description
All Cause Mortality
	Placebo (1st Stage)		Linagliptin 5mg (2nd-Extension Stage After Placebo)		Linagliptin 10mg (2nd-Extension Stage After Placebo)		Linagliptin 5mg (1st-2nd-Extension Stage)		Linagliptin 10mg (1st-2nd-Extension Stage)		Voglibose (1st-2nd Stage)		Linagliptin 5mg (Extension Stage After Voglibose)		Linagliptin 10mg (Extension Stage After Voglibose)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo (1st Stage)		Linagliptin 5mg (2nd-Extension Stage After Placebo)		Linagliptin 10mg (2nd-Extension Stage After Placebo)		Linagliptin 5mg (1st-2nd-Extension Stage)		Linagliptin 10mg (1st-2nd-Extension Stage)		Voglibose (1st-2nd Stage)		Linagliptin 5mg (Extension Stage After Voglibose)		Linagliptin 10mg (Extension Stage After Voglibose)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/80 (1.3%)		3/36 (8.3%)		1/38 (2.6%)		14/159 (8.8%)		10/160 (6.3%)		7/162 (4.3%)		3/71 (4.2%)		3/76 (3.9%)
Cardiac disorders
Acute coronary syndrome	0/80 (0%)		0/36 (0%)		1/38 (2.6%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Acute myocardial infarction	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Angina pectoris	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		2/162 (1.2%)		0/71 (0%)		0/76 (0%)
Angina unstable	0/80 (0%)		1/36 (2.8%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Arrhythmia	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Atrial fibrillation	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Cardiac failure congestive	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Coronary artery occlusion	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Endocrine disorders
Hyperthyroidism	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Eye disorders
Cataract	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		1/162 (0.6%)		0/71 (0%)		1/76 (1.3%)
Gastrointestinal disorders
Abdominal hernia	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Colonic polyp	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Gastric ulcer	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Haemorrhoids	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Inguinal hernia	1/80 (1.3%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Hepatobiliary disorders
Bile duct stone	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Cholangitis	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Infections and infestations
Bronchitis	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Herpes zoster	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		1/76 (1.3%)
Osteomyelitis	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Injury, poisoning and procedural complications
Airway burns	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Clavicle fracture	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Contusion	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Fall	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Road traffic accident	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		1/71 (1.4%)		0/76 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/80 (0%)		1/36 (2.8%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Back pain	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		1/71 (1.4%)		0/76 (0%)
Limb deformity	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		1/162 (0.6%)		0/71 (0%)		0/76 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer recurrent	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		1/76 (1.3%)
Gastric cancer	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Gastric cancer recurrent	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Large intestine carcinoma	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Lung neoplasm malignant	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		1/162 (0.6%)		0/71 (0%)		0/76 (0%)
Metastases to liver	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Pancreatic carcinoma	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Prostate cancer	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Nervous system disorders
Carpal tunnel syndrome	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		1/162 (0.6%)		0/71 (0%)		0/76 (0%)
Cerebral infarction	0/80 (0%)		1/36 (2.8%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		1/71 (1.4%)		0/76 (0%)
Cerebral haemorrhage	0/80 (0%)		0/36 (0%)		0/38 (0%)		1/159 (0.6%)		0/160 (0%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Renal and urinary disorders
Calculus ureteric	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		0/160 (0%)		1/162 (0.6%)		0/71 (0%)		0/76 (0%)
Nephrolithiasis	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Vascular disorders
Hypertension	0/80 (0%)		0/36 (0%)		0/38 (0%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	Placebo (1st Stage)		Linagliptin 5mg (2nd-Extension Stage After Placebo)		Linagliptin 10mg (2nd-Extension Stage After Placebo)		Linagliptin 5mg (1st-2nd-Extension Stage)		Linagliptin 10mg (1st-2nd-Extension Stage)		Voglibose (1st-2nd Stage)		Linagliptin 5mg (Extension Stage After Voglibose)		Linagliptin 10mg (Extension Stage After Voglibose)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/80 (28.8%)		19/36 (52.8%)		21/38 (55.3%)		101/159 (63.5%)		107/160 (66.9%)		83/162 (51.2%)		28/71 (39.4%)		31/76 (40.8%)
Eye disorders
Cataract	0/80 (0%)		0/36 (0%)		3/38 (7.9%)		2/159 (1.3%)		2/160 (1.3%)		2/162 (1.2%)		2/71 (2.8%)		1/76 (1.3%)
Gastrointestinal disorders
Abdominal pain upper	0/80 (0%)		1/36 (2.8%)		2/38 (5.3%)		3/159 (1.9%)		3/160 (1.9%)		2/162 (1.2%)		2/71 (2.8%)		1/76 (1.3%)
Constipation	5/80 (6.3%)		0/36 (0%)		4/38 (10.5%)		12/159 (7.5%)		12/160 (7.5%)		5/162 (3.1%)		0/71 (0%)		3/76 (3.9%)
Dental caries	0/80 (0%)		0/36 (0%)		2/38 (5.3%)		7/159 (4.4%)		5/160 (3.1%)		4/162 (2.5%)		1/71 (1.4%)		0/76 (0%)
Diarrhoea	1/80 (1.3%)		0/36 (0%)		0/38 (0%)		10/159 (6.3%)		6/160 (3.8%)		15/162 (9.3%)		0/71 (0%)		0/76 (0%)
Flatulence	1/80 (1.3%)		0/36 (0%)		1/38 (2.6%)		4/159 (2.5%)		7/160 (4.4%)		10/162 (6.2%)		0/71 (0%)		0/76 (0%)
Nausea	1/80 (1.3%)		2/36 (5.6%)		0/38 (0%)		1/159 (0.6%)		1/160 (0.6%)		1/162 (0.6%)		0/71 (0%)		1/76 (1.3%)
Infections and infestations
Nasopharyngitis	10/80 (12.5%)		10/36 (27.8%)		8/38 (21.1%)		60/159 (37.7%)		57/160 (35.6%)		36/162 (22.2%)		14/71 (19.7%)		16/76 (21.1%)
Rhinitis	0/80 (0%)		2/36 (5.6%)		2/38 (5.3%)		2/159 (1.3%)		3/160 (1.9%)		2/162 (1.2%)		1/71 (1.4%)		0/76 (0%)
Bronchitis	0/80 (0%)		1/36 (2.8%)		2/38 (5.3%)		7/159 (4.4%)		6/160 (3.8%)		4/162 (2.5%)		1/71 (1.4%)		0/76 (0%)
Cystitis	1/80 (1.3%)		0/36 (0%)		2/38 (5.3%)		3/159 (1.9%)		1/160 (0.6%)		4/162 (2.5%)		1/71 (1.4%)		2/76 (2.6%)
Gastroenteritis	1/80 (1.3%)		1/36 (2.8%)		2/38 (5.3%)		4/159 (2.5%)		3/160 (1.9%)		2/162 (1.2%)		3/71 (4.2%)		1/76 (1.3%)
Injury, poisoning and procedural complications
Contusion	1/80 (1.3%)		1/36 (2.8%)		2/38 (5.3%)		5/159 (3.1%)		4/160 (2.5%)		3/162 (1.9%)		0/71 (0%)		0/76 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	4/80 (5%)		3/36 (8.3%)		0/38 (0%)		7/159 (4.4%)		7/160 (4.4%)		7/162 (4.3%)		1/71 (1.4%)		4/76 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/80 (0%)		1/36 (2.8%)		2/38 (5.3%)		4/159 (2.5%)		3/160 (1.9%)		2/162 (1.2%)		0/71 (0%)		1/76 (1.3%)
Back pain	2/80 (2.5%)		1/36 (2.8%)		2/38 (5.3%)		11/159 (6.9%)		15/160 (9.4%)		6/162 (3.7%)		1/71 (1.4%)		4/76 (5.3%)
Spinal osteoarthritis	0/80 (0%)		2/36 (5.6%)		0/38 (0%)		1/159 (0.6%)		2/160 (1.3%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Nervous system disorders
Dizziness	0/80 (0%)		0/36 (0%)		2/38 (5.3%)		3/159 (1.9%)		2/160 (1.3%)		4/162 (2.5%)		1/71 (1.4%)		0/76 (0%)
Psychiatric disorders
Depression	0/80 (0%)		0/36 (0%)		2/38 (5.3%)		0/159 (0%)		1/160 (0.6%)		0/162 (0%)		0/71 (0%)		0/76 (0%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	0/80 (0%)		1/36 (2.8%)		2/38 (5.3%)		9/159 (5.7%)		10/160 (6.3%)		2/162 (1.2%)		2/71 (2.8%)		1/76 (1.3%)
Skin and subcutaneous tissue disorders
Eczema	0/80 (0%)		2/36 (5.6%)		1/38 (2.6%)		6/159 (3.8%)		5/160 (3.1%)		2/162 (1.2%)		1/71 (1.4%)		0/76 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.