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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003317-33 | EudraCT Number | EudraCT |
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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
The general aim of the present study is to investigate the impact of 4 weeks treatment with linagliptin (5 mg) on endothelial function in patients with type 2 diabetes mellitus. In the current trial this effect of linagliptin treatment on endothelial function will be compared against both the sulfonylurea glimepiride and against placebo, which has not been tested in a trial before; as also is the case for other DPP-4 inhibitors.
Besides placebo, glimepiride was chosen as a comparator, as it is one compound of the second most used oral antidiabetic drug class.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Linagliptin 5mg | Experimental | given once daily over 28 days |
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| Glimepiride | Active Comparator | given once daily in 1mg dosis over 7 days, following a titration step to 2mg and application for 21 days |
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| Placebo | Placebo Comparator | given once daily over 28 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo matching Glimepiride |
| |
| Linagliptin |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28 | Endothelial function under fasted condition was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline. | baseline and day 28 for each treatment arm |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Flow Mediated Vasodilation (FMD) 2 h Post Meal on Day 28 | Endothelial function 2 hours post meal was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline. | baseline and day 28 for each treatment arm |
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Inclusion criteria:
Type 2 diabetic male and female patients according to the following criteria:
Based upon a complete medical history and clinical laboratory tests
Age >= 18 and Age <= 65 years
Body mass index >= 25 <= 35 kg/m2
HbA1c <= 7.5%
Treatment with metformin (=1500 mg daily) for <= 3 months
Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
For female patients of childbearing potential:
Use of acceptable method of contraception (Pearl-Index <1).
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1218.105.001 Boehringer Ingelheim Investigational Site | Neuss | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28109295 | Derived | Jax T, Stirban A, Terjung A, Esmaeili H, Berk A, Thiemann S, Chilton R, von Eynatten M, Marx N. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc Diabetol. 2017 Jan 21;16(1):13. doi: 10.1186/s12933-016-0493-3. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Pbo/ G1-4/ L 5 | Placebo tablet once daily over 28 days/ Glimepiride 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days/ Linagliptin 1 tablet (5 mg) once daily for 28 days |
| FG001 | L 5/ G 1-4/ Pbo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 Including Washout |
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| Drug |
given once daily for 28 days |
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| Placebo | Drug | Placebo matching Linagliptin |
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| Placebo | Drug | Placebo matching Linagliptin |
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| Placebo | Drug | Placebo matching Glimepiride |
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| Glimepiride | Drug | 1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days) |
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| Change From Baseline in 2 Hours Post Meal Endothelial Independent Vasodilation (EIDV) on Day 28 |
Endothelial function 2h post-meal was measured by endothelial independent vasodilation (EIDV). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline. |
| baseline and day 28 for each treatment arm |
| Number of Patients With Adverse Events | Number of patients with any adverse events | up to 20 weeks |
Linagliptin 1 tablet (5 mg) once daily for 28 days/ Glimepiride 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days/ Placebo tablet once daily over 28 days |
| FG002 | G 1-4/ L 5/ Pbo | Glimepiride 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days/ Linagliptin 1 tablet (5 mg) once daily for 28 days/ Placebo tablet once daily over 28 days |
| FG003 | G1-4/ Pbo/ L 5 | Glimepiride 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days/ Placebo tablet once daily over 28 days/ Linagliptin 1 tablet (5 mg) once daily for 28 days |
| FG004 | Pbo/ L 5/ G1-4 | Placebo tablet once daily over 28 days/ Linagliptin 1 tablet (5 mg) once daily for 28 days/ Glimepiride 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days |
| FG005 | L 5/ Pbo/ G1-4/ | Linagliptin 1 tablet (5 mg) once daily for 28 days/ Placebo tablet once daily over 28 days/ Glimepiride 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 Including Washout |
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| Period 3 Including Washout |
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TS (treated set) - included all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Total Participants | All study participants |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28 | Endothelial function under fasted condition was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline. | Efficacy set (ES)- included all patients of the TS who provided at least 1 observation for at least 1 primary, secondary, or other efficacy endpoint without important protocol violations relevant for the statistical evaluation of these endpoints. | Posted | Geometric Mean | 90% Confidence Interval | percentage | baseline and day 28 for each treatment arm |
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| Secondary | Change From Baseline in Flow Mediated Vasodilation (FMD) 2 h Post Meal on Day 28 | Endothelial function 2 hours post meal was measured with flow mediated vasodilation (FMD). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline. | Posted | Geometric Mean | 90% Confidence Interval | Percentage | baseline and day 28 for each treatment arm |
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| Secondary | Change From Baseline in 2 Hours Post Meal Endothelial Independent Vasodilation (EIDV) on Day 28 | Endothelial function 2h post-meal was measured by endothelial independent vasodilation (EIDV). The change from baseline was calculated as the value on Day 28 divided by the respective value at baseline. | Efficacy set (ES)- included all patients of the TS who provided at least 1 observation for at least 1 primary, secondary, or other efficacy endpoint without important protocol violations relevant for the statistical evaluation of these endpoints. | Posted | Mean | 90% Confidence Interval | percentage | baseline and day 28 for each treatment arm |
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| Secondary | Number of Patients With Adverse Events | Number of patients with any adverse events | Treated set (TS) | Posted | Number | participants | up to 20 weeks |
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28 days treatment period + 7 days residual effect period
The adverse events occurred during residual effect period (REP) were included in the frequencies.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Linagliptin 5 mg | Linagliptin: 1 tablet (5 mg) once daily for 28 days | 0 | 40 | 6 | 40 | ||
| EG001 | Glimepiride 1-4 mg | Glimepiride: 1 tablet (1 mg) once daily for 7 days followed by uptitration to 2 to 4 mg once daily within next 21 days | 0 | 41 | 20 | 41 | ||
| EG002 | Placebo | Placebo: matching Linagliptin or Glimepiride given once daily over 28 days | 0 | 40 | 9 | 40 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000069476 | Linagliptin |
| C057619 | glimepiride |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011799 | Quinazolines |
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| Geometric mean ratio (net) |
| 0.884 |
| 2-Sided |
| 90 |
| 0.632 |
| 1.235 |
| No |
| Superiority or Other |
| ANOVA | 0.9989 | Geometric mean ratio (net) | 1.000 | 2-Sided | 90 | 0.715 | 1.397 | No | Superiority or Other |
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| Participants |
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| OG005 | Rep - Placebo | Residual effect period - Placebo |
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