Trial to Assess the Influence of 4 Weeks' Treatment With Linagliptin as Compared to Glimepiride and Placebo on Endothelial Function in Patients With Type 2 Diabetes Using FMD (Flow-Mediated Vasodilation)

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Randomized, Three Period Cross Over, Double Blind, Double Dummy Study in Type 2 Diabetic Patients to Assess the Endothelial Effects of Linagliptin, Glimepiride and Placebo Therapy for 28 Days ('ENDOTHELINA')

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01703286
• Other study ID #: 1218.105
• Secondary ID: 2012-003317-33
• Status: Completed
• Phase: Phase 1
• First received: October 1, 2012
• Last updated: January 12, 2015
• Start date: October 2012
• Est. completion date: January 2014

Study information

• Verified date: January 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Ministry of Food, Agriculture and Consumer Protection
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

1. Type 2 diabetic male and female patients according to the following criteria:

Based upon a complete medical history and clinical laboratory tests

2. Age >= 18 and Age <= 65 years

3. Body mass index >= 25 <= 35 kg/m2

4. HbA1c <= 7.5%

5. Treatment with metformin (=1500 mg daily) for <= 3 months

6. 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:

7. Use of acceptable method of contraception (Pearl-Index <1).

Exclusion criteria:

1. Treatment with any glucose-lowering drug except for metformin within prior 3 months.

2. Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance.

3. Any evidence of a clinically relevant acute concomitant disease

4. History of cardiovascular disease (e.g. coronary artery disease history of acute myocard infarction or stroke, peripheral vascular disease).

5. History of major diabetic complications (e.g. nephropathy, retinopathy)

6. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, immunological or hormonal disorders (except: hypertension treated with angiotensin receptor blocker or angiotensin-converting-enzyme inhibitors, hyperlipidemia with statin therapy, thyroid hormone replacement therapy, all stable for at least three months prior to screening).

7. Surgery of the gastrointestinal tract (except appendectomy).

8. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders.

9. History of relevant orthostatic hypotension, fainting spells or blackouts.

10. Chronic or relevant acute infections.

11. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).

12. Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial.

13. Participation in another trial with an investigational drug within one month prior to administration or during the trial.

14. Smoker (>= 1 cigarettes or >= 1 cigars or >= 1 pipes/day).

15. Alcohol abuse (more than 60 g/day).

16. Drug abuse.

17. Blood donation (more than 100 mL within four weeks prior to administration or during the trial).

18. Excessive physical activities (within one week prior to administration or during the trial).

19. Any laboratory value outside the reference range that is of clinical relevance.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Placebo
Placebo matching Glimepiride
• Linagliptin
given once daily for 28 days
• Placebo
Placebo matching Linagliptin
• Placebo
Placebo matching Linagliptin
• Placebo
Placebo matching Glimepiride
• Glimepiride
1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days)

Locations

Country	Name	City	State
Germany	1218.105.001 Boehringer Ingelheim Investigational Site	Neuss

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	baseline and day 28 for each treatment arm	No
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.	baseline and day 28 for each treatment arm	No
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.	baseline and day 28 for each treatment arm	No
Secondary	Number of Patients With Adverse Events	Number of patients with any adverse events	up to 20 weeks	No

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