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)

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Linagliptin; Drug: Glimepiride; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01703286

2012-003317-33 (EudraCT Number)

1218.105

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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42 participants in 3 patient groups, including a placebo group

Linagliptin 5mg

Experimental group

Description:

given once daily over 28 days

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Linagliptin

Drug: Placebo

Glimepiride

Active Comparator group

Description:

given once daily in 1mg dosis over 7 days, following a titration step to 2mg and application for 21 days

Treatment:

Drug: Placebo

Drug: Glimepiride

Drug: Placebo

Drug: Placebo

Drug: Placebo

Placebo

Placebo Comparator group

Description:

given once daily over 28 days

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo