Safety and Efficacy in Type 2 Diabetic Patients With Severe Chronic Renal Impairment, 5 mg BI 1356 (Linagliptin) vs. Placebo, Insulin Background Inclusive
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT00800683
Collaborator
(none)
133
53
2
2.5
Study Details
Study Description
Brief Summary
to determine safety, efficacy and tolerability of BI 1356 versus placebo
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
133 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
Safety in Type 2 Diabetic Patients With Severe Chronic Renal Impairment, 5 mg BI 1356 vs. Placebo, DB, Parallel Group, Randomized, Insulin Background Inclusive
Study Start Date
:
Dec 1, 2008
Actual Primary Completion Date
:
Jan 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BI 1356 patient to receive a tablet containing BI 1356 once daily |
Drug: BI 1356
BI 1356 dosed once daily
|
| Placebo Comparator: placebo patient to receive a tablet identical to BI 1356 once daily |
Drug: placebo
placebo matching BI 1356 taken once daily
|
Outcome Measures
Primary Outcome Measures
- HbA1c Change From Baseline at Week 12 [Baseline and Week 12]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline continuous HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
Secondary Outcome Measures
- HbA1c Change From Baseline at Week 52 [Baseline and Week 52]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- HbA1c Change From Baseline at Week 18 [Baseline and Week 18]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- HbA1c Change From Baseline at Week 24 [Baseline and Week 24]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- HbA1c Change From Baseline at Week 30 [Baseline and Week 30]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- HbA1c Change From Baseline at Week 36 [Baseline and Week 36]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 36 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- HbA1c Change From Baseline at Week 42 [Baseline and Week 42]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 42 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- HbA1c Change From Baseline at Week 48 [Baseline and Week 48]
HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 48 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.
- The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 52 Weeks of Treatment [Baseline and Week 52]
The percentage of patients with an HbA1c value below 6.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=6.5%
- The Occurrence of a Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 52 Weeks of Treatment [Baseline and Week 52]
The percentage of patients with an HbA1c value below 7.0% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=7%.
- Percentage of Patients With HbA1c Lowering by 0.5% at Week 52 [Baseline and Week 52]
The percentage of patients with an HbA1c reduction from baseline >=0.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF).
- FPG Change From Baseline at Week 12 [Baseline and Week 12]
This change from baseline reflects the week 12 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at Week 18 [Baseline and Week 18]
Model includes treatment, continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at Week 24 [Baseline and Week 24]
This change from baseline reflects the week 24 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at Week 30 [Baseline and Week 30]
This change from baseline reflects the week 30 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at Week 36 [Baseline and Week 36]
This change from baseline reflects the week 36 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at Week 42 [Baseline and Week 42]
This change from baseline reflects the week 42 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at Week 48 [Baseline and Week 48]
This change from baseline reflects the week 48 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs
- FPG Change From Baseline at week52 [Baseline and Week 52]
This change from baseline reflects the week 52 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs
- Change From Baseline in Antidiabetic Background Therapy Dose at 52 Weeks Compared to Baseline and Over Time [Baseline and Week 52]
Number of patients with at least one change in daily dose, determined by at least a 10% increase in insulin.
- Clinically Relevant Drug-related Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG [first administration of randomised treatment to ....]
Clinically relevant drug-related abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as adverse events.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Male and female patients with type 2 diabetes and with glomerular filtration rate (GFR) <30 ml/min, who are not on chronic dialysis.
-
Insufficient glycemic control (hemoglobin A1c (HbA1c) between 7.0% and 10.0%)
-
Age 18 or over and not older than 80 years
Exclusion criteria:
-
Treatment with any other anti diabetic drug other than insulin and/or sulphonylurea within 3 months prior to informed consent
-
Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent
-
Unstable or acute congestive heart failure
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1218.43.10027 Boehringer Ingelheim Investigational Site | Phoenix | Arizona | United States | |
| 2 | 1218.43.10011 Boehringer Ingelheim Investigational Site | Chula Vista | California | United States | |
| 3 | 1218.43.10006 Boehringer Ingelheim Investigational Site | Riverside | California | United States | |
| 4 | 1218.43.10021 Boehringer Ingelheim Investigational Site | Whittier | California | United States | |
| 5 | 1218.43.10013 Boehringer Ingelheim Investigational Site | Pembroke Pines | Florida | United States | |
| 6 | 1218.43.10009 Boehringer Ingelheim Investigational Site | West Palm Beach | Florida | United States | |
| 7 | 1218.43.10018 Boehringer Ingelheim Investigational Site | Decatur | Georgia | United States | |
| 8 | 1218.43.10022 Boehringer Ingelheim Investigational Site | Chicago | Illinois | United States | |
| 9 | 1218.43.10015 Boehringer Ingelheim Investigational Site | Shreveport | Louisiana | United States | |
| 10 | 1218.43.10016 Boehringer Ingelheim Investigational Site | Kansas City | Missouri | United States | |
| 11 | 1218.43.10004 Boehringer Ingelheim Investigational Site | Bronx | New York | United States | |
| 12 | 1218.43.10003 Boehringer Ingelheim Investigational Site | Great Neck | New York | United States | |
| 13 | 1218.43.10020 Boehringer Ingelheim Investigational Site | Winston-Salem | North Carolina | United States | |
| 14 | 1218.43.10019 Boehringer Ingelheim Investigational Site | Delaware | Ohio | United States | |
| 15 | 1218.43.10008 Boehringer Ingelheim Investigational Site | Mentor | Ohio | United States | |
| 16 | 1218.43.10005 Boehringer Ingelheim Investigational Site | Bethlehem | Pennsylvania | United States | |
| 17 | 1218.43.10007 Boehringer Ingelheim Investigational Site | Carlisle | Pennsylvania | United States | |
| 18 | 1218.43.10001 Boehringer Ingelheim Investigational Site | Providence | Rhode Island | United States | |
| 19 | 1218.43.10025 Boehringer Ingelheim Investigational Site | Aiken | South Carolina | United States | |
| 20 | 1218.43.10023 Boehringer Ingelheim Investigational Site | Austin | Texas | United States | |
| 21 | 1218.43.10024 Boehringer Ingelheim Investigational Site | Austin | Texas | United States | |
| 22 | 1218.43.10014 Boehringer Ingelheim Investigational Site | Dallas | Texas | United States | |
| 23 | 1218.43.10017 Boehringer Ingelheim Investigational Site | Lufkin | Texas | United States | |
| 24 | 1218.43.10010 Boehringer Ingelheim Investigational Site | Tacoma | Washington | United States | |
| 25 | 1218.43.61009 Boehringer Ingelheim Investigational Site | Gosford | New South Wales | Australia | |
| 26 | 1218.43.61010 Boehringer Ingelheim Investigational Site | Auchenflower | Queensland | Australia | |
| 27 | 1218.43.61006 Boehringer Ingelheim Investigational Site | Kippa Ring | Queensland | Australia | |
| 28 | 1218.43.61007 Boehringer Ingelheim Investigational Site | Reservoir | Victoria | Australia | |
| 29 | 1218.43.61011 Boehringer Ingelheim Investigational Site | Richmond | Victoria | Australia | |
| 30 | 1218.43.61005 Boehringer Ingelheim Investigational Site | Adelaide, SA | Australia | ||
| 31 | 1218.43.61002 Boehringer Ingelheim Investigational Site | Herston, QLD | Australia | ||
| 32 | 1218.43.85201 Boehringer Ingelheim Investigational Site | Hong Kong | Hong Kong | ||
| 33 | 1218.43.85203 Boehringer Ingelheim Investigational Site | New Territories | Hong Kong | ||
| 34 | 1218.43.97008 Boehringer Ingelheim Investigational Site | Afula | Israel | ||
| 35 | 1218.43.97005 Boehringer Ingelheim Investigational Site | Ashkelon | Israel | ||
| 36 | 1218.43.97003 Boehringer Ingelheim Investigational Site | Haifa | Israel | ||
| 37 | 1218.43.97004 Boehringer Ingelheim Investigational Site | Jerusalem | Israel | ||
| 38 | 1218.43.97009 Boehringer Ingelheim Investigational Site | Jerusalem | Israel | ||
| 39 | 1218.43.97002 Boehringer Ingelheim Investigational Site | Kfar Saba | Israel | ||
| 40 | 1218.43.97007 Boehringer Ingelheim Investigational Site | Nahariya | Israel | ||
| 41 | 1218.43.97001 Boehringer Ingelheim Investigational Site | Safed | Israel | ||
| 42 | 1218.43.97006 Boehringer Ingelheim Investigational Site | Tel Aviv | Israel | ||
| 43 | 1218.43.64001 Boehringer Ingelheim Investigational Site | Auckland | New Zealand | ||
| 44 | 1218.43.64003 Boehringer Ingelheim Investigational Site | Christchurch | New Zealand | ||
| 45 | 1218.43.64004 Boehringer Ingelheim Investigational Site | Takpuna | New Zealand | ||
| 46 | 1218.43.64002 Boehringer Ingelheim Investigational Site | Tauranga | New Zealand | ||
| 47 | 1218.43.38004 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 48 | 1218.43.38003 Boehringer Ingelheim Investigational Site | Kharkov | Ukraine | ||
| 49 | 1218.43.38006 Boehringer Ingelheim Investigational Site | Kharkov | Ukraine | ||
| 50 | 1218.43.38005 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 51 | 1218.43.38007 Boehringer Ingelheim Investigational Site | Lugansk | Ukraine | ||
| 52 | 1218.43.38008 Boehringer Ingelheim Investigational Site | Ternopil | Ukraine | ||
| 53 | 1218.43.38002 Boehringer Ingelheim Investigational Site | Zaporizhzhya | Ukraine |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00800683
Other Study ID Numbers:
- 1218.43
- 2008-001569-27
First Posted:
Dec 2, 2008
Last Update Posted:
May 20, 2014
Last Verified:
May 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Period Title: Overall Study | ||
| STARTED | 65 | 68 |
| COMPLETED | 48 | 49 |
| NOT COMPLETED | 17 | 19 |
Baseline Characteristics
| Arm/Group Title | Placebo | Linagliptin (BI 1356) | Total |
|---|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg | Total of all reporting groups |
| Overall Participants | 65 | 68 | 133 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.9
(9.6)
|
64.0
(10.9)
|
64.4
(10.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
30
46.2%
|
23
33.8%
|
53
39.8%
|
| Male |
35
53.8%
|
45
66.2%
|
80
60.2%
|
| Glycosylated haemoglobin (HbA1c) at baseline (percentage) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [percentage] |
8.2
(0.9)
|
8.2
(1.1)
|
8.2
(1.0)
|
| Fasting plasma glucose (FPG) at baseline (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
160.1
(65.4)
|
149.5
(79.5)
|
154.6
(72.9)
|
| Body Mass Index (BMI) Continuous (kg/m²) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg/m²] |
31.7
(5.9)
|
32.3
(5.9)
|
32.0
(5.8)
|
Outcome Measures
| Title | HbA1c Change From Baseline at Week 12 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline continuous HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
-0.15
(0.15)
|
-0.76
(0.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | For patients who received rescue medication during the course of the trial, the Oracle Clinical (OC) technique was utilised for all efficacy endpoints and the values were set to missing after the rescue medication was administered. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.60 | |
| Confidence Interval |
() 95% -0.89 to -0.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 52 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
0.01
(0.16)
|
-0.71
(0.15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.72 | |
| Confidence Interval |
() 95% -1.03 to -0.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 18 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 18 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
0.04
(0.14)
|
-0.57
(0.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -0.61 | |
| Confidence Interval |
() 95% -0.90 to -0.33 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 24 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
0.04
(0.14)
|
-0.64
(0.13)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.68 | |
| Confidence Interval |
() 95% -0.96 to -0.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 30 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
0.04
(0.16)
|
-0.67
(0.16)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.72 | |
| Confidence Interval |
() 95% -1.05 to -0.39 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 36 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 36 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
0.03
(0.16)
|
-0.72
(0.15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.75 | |
| Confidence Interval |
() 95% -1.06 to -0.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 42 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 42 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
-0.08
(0.16)
|
-0.73
(0.15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -0.64 | |
| Confidence Interval |
() 95% -0.96 to -0.33 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| Estimation Comments | ||
| Title | HbA1c Change From Baseline at Week 48 |
|---|---|
| Description | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 48 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) included all treated and randomised participants with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Least Squares Mean (Standard Error) [Percent] |
-0.04
(0.15)
|
-0.77
(0.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.73 | |
| Confidence Interval |
() 95% -1.02 to -0.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
| Title | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 52 Weeks of Treatment |
|---|---|
| Description | The percentage of patients with an HbA1c value below 6.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=6.5% |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS with baseline HbA1c>=6.5%. Non-completers were considered as failure imputation (NCF). |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Number [Percentage of patients] |
0
|
6.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1199 |
| Comments | P-value calculated using a Fisher's exact Test. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | The Occurrence of a Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 52 Weeks of Treatment |
|---|---|
| Description | The percentage of patients with an HbA1c value below 7.0% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=7%. |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS with baseline HbA1c>=7.0%. Non-completers were considered as failure imputation (NCF). |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 61 | 61 |
| Number [Percentage of patients] |
9.8
|
18.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | Linagliptin vs Placebo. The odds-ratio is based on a logistic regression model including baseline HbA1c, previous anti-diabetic medication and creatinine clearance | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2225 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.103 | |
| Confidence Interval |
() 95% 0.003 to 3.978 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Patients With HbA1c Lowering by 0.5% at Week 52 |
|---|---|
| Description | The percentage of patients with an HbA1c reduction from baseline >=0.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 62 | 66 |
| Number [Percentage of patients] |
11.3
|
27.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | Linagliptin vs Placebo. The odds-ratio is based on a logistic regression model including baseline HbA1c, previous anti-diabetic medication and creatinine clearance | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8927 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.816 | |
| Confidence Interval |
(2-Sided) 95% 0.042 to 15.756 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 12 |
|---|---|
| Description | This change from baseline reflects the week 12 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-7.08
(11.08)
|
-8.81
(10.66)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8802 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.73 | |
| Confidence Interval |
() 95% -24.36 to 20.91 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 11.43 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 18 |
|---|---|
| Description | Model includes treatment, continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 18 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-12.72
(7.94)
|
-14.97
(7.64)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7848 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.24 | |
| Confidence Interval |
() 95% -18.47 to 13.98 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.19 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 24 |
|---|---|
| Description | This change from baseline reflects the week 24 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-6.22
(7.84)
|
-16.93
(7.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1878 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -10.72 | |
| Confidence Interval |
() 95% -26.74 to 5.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.09 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 30 |
|---|---|
| Description | This change from baseline reflects the week 30 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-14.54
(7.68)
|
-10.12
(7.39)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5781 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.42 | |
| Confidence Interval |
() 95% -11.28 to 20.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.92 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 36 |
|---|---|
| Description | This change from baseline reflects the week 36 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-11.29
(8.53)
|
-20.53
(8.20)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2954 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.24 | |
| Confidence Interval |
() 95% -26.67 to 8.18 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.80 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 42 |
|---|---|
| Description | This change from baseline reflects the week 42 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-13.25
(8.02)
|
-8.88
(7.71)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5984 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.37 | |
| Confidence Interval |
() 95% -12.02 to 20.75 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.27 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at Week 48 |
|---|---|
| Description | This change from baseline reflects the week 48 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-10.52
(8.26)
|
-3.45
(7.95)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4085 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.07 | |
| Confidence Interval |
() 95% -9.82 to 23.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.53 |
|
| Estimation Comments | ||
| Title | FPG Change From Baseline at week52 |
|---|---|
| Description | This change from baseline reflects the week 52 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value. |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 57 | 63 |
| Least Squares Mean (Standard Error) [mg/dL] |
-6.81
(7.92)
|
-5.47
(7.62)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Linagliptin (BI 1356) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8698 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.34 | |
| Confidence Interval |
() 95% -14.84 to 17.52 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.17 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Antidiabetic Background Therapy Dose at 52 Weeks Compared to Baseline and Over Time |
|---|---|
| Description | Number of patients with at least one change in daily dose, determined by at least a 10% increase in insulin. |
| Time Frame | Baseline and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated Set |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 65 | 68 |
| Week 1- Week12 |
11
16.9%
|
17
25%
|
| Week 12 - Week 52 |
29
44.6%
|
24
35.3%
|
| Overall (Baseline -Week 52) |
33
50.8%
|
32
47.1%
|
| Title | Clinically Relevant Drug-related Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG |
|---|---|
| Description | Clinically relevant drug-related abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as adverse events. |
| Time Frame | first administration of randomised treatment to .... |
Outcome Measure Data
| Analysis Population Description |
|---|
| Clinically relevant drug-related abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG |
| Arm/Group Title | Placebo | Linagliptin (BI 1356) |
|---|---|---|
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg |
| Measure Participants | 65 | 68 |
| Cardiac disorders - Tachycardia |
1
1.5%
|
0
0%
|
| Blood amylase increased |
1
1.5%
|
0
0%
|
| Blood creatine phosphokinase MB increased |
1
1.5%
|
1
1.5%
|
| Blood creatine phosphokinase increased |
1
1.5%
|
2
2.9%
|
| Glycosylated haemoglobin increased |
0
0%
|
1
1.5%
|
Adverse Events
| Time Frame | 52 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The period of 52 weeks was the maximum of study treatment. Patients were allowed to remain on study medication for up to 52 weeks. | |||
| Arm/Group Title | Placebo | Linagliptin (BI 1356) | ||
| Arm/Group Description | Patients randomized to receive treatment with matching placebo | Patients randomized to receive treatment with Linagliptin 5mg | ||
All Cause Mortality |
||||
| Placebo | Linagliptin (BI 1356) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Linagliptin (BI 1356) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/65 (41.5%) | 25/68 (36.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/65 (1.5%) | 0/68 (0%) | ||
| Haemorrhagic anaemia | 0/65 (0%) | 1/68 (1.5%) | ||
| Nephrogenic anaemia | 0/65 (0%) | 1/68 (1.5%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 0/65 (0%) | 1/68 (1.5%) | ||
| Acute myocardial infarction | 1/65 (1.5%) | 3/68 (4.4%) | ||
| Angina pectoris | 3/65 (4.6%) | 3/68 (4.4%) | ||
| Angina unstable | 1/65 (1.5%) | 0/68 (0%) | ||
| Aortic valve disease | 0/65 (0%) | 0/68 (0%) | ||
| Arrhythmia | 1/65 (1.5%) | 0/68 (0%) | ||
| Atrial fibrillation | 0/65 (0%) | 2/68 (2.9%) | ||
| Atrioventricular block second degree | 1/65 (1.5%) | 0/68 (0%) | ||
| Cardiac arrest | 0/65 (0%) | 2/68 (2.9%) | ||
| Cardiac failure acute | 0/65 (0%) | 2/68 (2.9%) | ||
| Cardiac failure congestive | 1/65 (1.5%) | 2/68 (2.9%) | ||
| Cardio-respiratory arrest | 1/65 (1.5%) | 0/68 (0%) | ||
| Coronary artery disease | 1/65 (1.5%) | 0/68 (0%) | ||
| Coronary artery stenosis | 0/65 (0%) | 2/68 (2.9%) | ||
| Left ventricular failure | 0/65 (0%) | 1/68 (1.5%) | ||
| Mitral valve incompetence | 0/65 (0%) | 1/68 (1.5%) | ||
| Myocardial infarction | 2/65 (3.1%) | 1/68 (1.5%) | ||
| Ventricular hypokinesia | 0/65 (0%) | 1/68 (1.5%) | ||
| Ventricular tachycardia | 0/65 (0%) | 1/68 (1.5%) | ||
| Cardiac death | 1/65 (1.5%) | 0/68 (0%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo positional | 0/65 (0%) | 1/68 (1.5%) | ||
| Endocrine disorders | ||||
| Parathyroid gland enlargement | 0/65 (0%) | 1/68 (1.5%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain upper | 2/65 (3.1%) | 0/68 (0%) | ||
| Constipation | 1/65 (1.5%) | 0/68 (0%) | ||
| Gastritis | 1/65 (1.5%) | 0/68 (0%) | ||
| Gastritis haemorrhagic | 0/65 (0%) | 0/68 (0%) | ||
| Megacolon | 0/65 (0%) | 0/68 (0%) | ||
| Vomiting | 1/65 (1.5%) | 0/68 (0%) | ||
| General disorders | ||||
| Death | 0/65 (0%) | 1/68 (1.5%) | ||
| Pyrexia | 1/65 (1.5%) | 0/68 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/65 (0%) | 0/68 (0%) | ||
| Cholecystitis acute | 0/65 (0%) | 1/68 (1.5%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 1/65 (1.5%) | 0/68 (0%) | ||
| Infections and infestations | ||||
| Bronchitis | 1/65 (1.5%) | 0/68 (0%) | ||
| Catheter site infection | 0/65 (0%) | 1/68 (1.5%) | ||
| Cellulitis | 0/65 (0%) | 1/68 (1.5%) | ||
| Clostridium difficile colitis | 0/65 (0%) | 0/68 (0%) | ||
| Device related sepsis | 1/65 (1.5%) | 1/68 (1.5%) | ||
| Gangrene | 0/65 (0%) | 0/68 (0%) | ||
| Lobar pneumonia | 1/65 (1.5%) | 0/68 (0%) | ||
| Osteomyelitis | 0/65 (0%) | 1/68 (1.5%) | ||
| Pneumonia | 0/65 (0%) | 3/68 (4.4%) | ||
| Sepsis | 0/65 (0%) | 1/68 (1.5%) | ||
| Septic shock | 0/65 (0%) | 0/68 (0%) | ||
| Staphylococcal sepsis | 1/65 (1.5%) | 0/68 (0%) | ||
| Urinary tract infection | 1/65 (1.5%) | 1/68 (1.5%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 0/65 (0%) | 2/68 (2.9%) | ||
| Femur fracture | 0/65 (0%) | 1/68 (1.5%) | ||
| Humerus fracture | 0/65 (0%) | 1/68 (1.5%) | ||
| Investigations | ||||
| Occult blood positive | 1/65 (1.5%) | 0/68 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/65 (0%) | 1/68 (1.5%) | ||
| Fluid overload | 0/65 (0%) | 1/68 (1.5%) | ||
| Hyperkalaemia | 3/65 (4.6%) | 0/68 (0%) | ||
| Hypoglycaemia | 1/65 (1.5%) | 2/68 (2.9%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Lumbar spinal stenosis | 1/65 (1.5%) | 0/68 (0%) | ||
| Musculoskeletal chest pain | 0/65 (0%) | 1/68 (1.5%) | ||
| Rhabdomyolysis | 0/65 (0%) | 1/68 (1.5%) | ||
| Trigger finger | 1/65 (1.5%) | 0/68 (0%) | ||
| Nervous system disorders | ||||
| Carotid artery stenosis | 1/65 (1.5%) | 0/68 (0%) | ||
| Cerebrovascular accident | 2/65 (3.1%) | 1/68 (1.5%) | ||
| Syncope | 2/65 (3.1%) | 0/68 (0%) | ||
| Transient ischaemic attack | 1/65 (1.5%) | 0/68 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure | 1/65 (1.5%) | 0/68 (0%) | ||
| Renal failure acute | 3/65 (4.6%) | 5/68 (7.4%) | ||
| Renal failure chronic | 1/65 (1.5%) | 0/68 (0%) | ||
| Renal impairment | 2/65 (3.1%) | 3/68 (4.4%) | ||
| Urinary retention | 0/65 (0%) | 0/68 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 0/65 (0%) | 1/68 (1.5%) | ||
| Acute respiratory failure | 0/65 (0%) | 0/68 (0%) | ||
| Chronic obstructive pulmonary disease | 0/65 (0%) | 0/68 (0%) | ||
| Dyspnoea | 1/65 (1.5%) | 0/68 (0%) | ||
| Dyspnoea paroxysmal nocturnal | 0/65 (0%) | 1/68 (1.5%) | ||
| Haemoptysis | 0/65 (0%) | 1/68 (1.5%) | ||
| Lung infiltration | 1/65 (1.5%) | 0/68 (0%) | ||
| Pleural effusion | 0/65 (0%) | 0/68 (0%) | ||
| Pleuritic pain | 1/65 (1.5%) | 0/68 (0%) | ||
| Pulmonary congestion | 3/65 (4.6%) | 1/68 (1.5%) | ||
| Pulmonary embolism | 1/65 (1.5%) | 0/68 (0%) | ||
| Pulmonary hilar enlargement | 0/65 (0%) | 1/68 (1.5%) | ||
| Pulmonary oedema | 1/65 (1.5%) | 0/68 (0%) | ||
| Respiratory failure | 0/65 (0%) | 1/68 (1.5%) | ||
| Surgical and medical procedures | ||||
| Arteriovenous fistula operation | 0/65 (0%) | 1/68 (1.5%) | ||
| Vascular disorders | ||||
| Hypertensive crisis | 0/65 (0%) | 1/68 (1.5%) | ||
| Ischaemia | 0/65 (0%) | 1/68 (1.5%) | ||
| Peripheral ischaemia | 1/65 (1.5%) | 0/68 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Linagliptin (BI 1356) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 50/65 (76.9%) | 61/68 (89.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 4/65 (6.2%) | 3/68 (4.4%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 3/65 (4.6%) | 8/68 (11.8%) | ||
| Diarrhoea | 6/65 (9.2%) | 10/68 (14.7%) | ||
| Nausea | 1/65 (1.5%) | 5/68 (7.4%) | ||
| General disorders | ||||
| Oedema peripheral | 7/65 (10.8%) | 7/68 (10.3%) | ||
| Infections and infestations | ||||
| Bronchitis | 1/65 (1.5%) | 4/68 (5.9%) | ||
| Influenza | 1/65 (1.5%) | 4/68 (5.9%) | ||
| Nasopharyngitis | 3/65 (4.6%) | 6/68 (8.8%) | ||
| Upper respiratory tract infection | 7/65 (10.8%) | 5/68 (7.4%) | ||
| Urinary tract infection | 7/65 (10.8%) | 5/68 (7.4%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 4/65 (6.2%) | 2/68 (2.9%) | ||
| Investigations | ||||
| Blood creatine phosphokinase increased | 7/65 (10.8%) | 7/68 (10.3%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperglycaemia | 23/65 (35.4%) | 19/68 (27.9%) | ||
| Hyperkalaemia | 14/65 (21.5%) | 21/68 (30.9%) | ||
| Hypoglycaemia | 32/65 (49.2%) | 43/68 (63.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 4/65 (6.2%) | 4/68 (5.9%) | ||
| Back pain | 5/65 (7.7%) | 4/68 (5.9%) | ||
| Muscle spasms | 2/65 (3.1%) | 5/68 (7.4%) | ||
| Pain in extremity | 3/65 (4.6%) | 4/68 (5.9%) | ||
| Nervous system disorders | ||||
| Headache | 4/65 (6.2%) | 2/68 (2.9%) | ||
| Renal and urinary disorders | ||||
| Renal impairment | 2/65 (3.1%) | 8/68 (11.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/65 (7.7%) | 3/68 (4.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 6/65 (9.2%) | 3/68 (4.4%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Other - 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.
Results Point of Contact
| Name/Title | Boehringer Ingelheim Call Center |
|---|---|
| Organization | Boehringer Ingelheim Pharmaceuticals |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00800683
Other Study ID Numbers:
- 1218.43
- 2008-001569-27
First Posted:
Dec 2, 2008
Last Update Posted:
May 20, 2014
Last Verified:
May 1, 2014