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)

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01703286
First received: October 1, 2012
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Placebo
Drug: Linagliptin
Drug: Glimepiride
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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')

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline in endothelial function as measured with flow mediated vasodilation (FMD) at baseline (fasting), and on day 28 (fasting) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in endothelial independent vasodilation (EIDV) at baseline (2 h post meal), and on day 28 (2 h post meal) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: up to 20 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in endothelial function as measured with flow mediated vasodilation (FMD) at baseline (2 h post meal), and on day 28 (2 h post meal) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
  • Number of patients with hepatic injury [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]
  • Number of patients with hypersensitivity reactions [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]
  • Number of patients with skin lesions [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]
  • Number of patients with renal adverse events [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]
  • Number of patients with Pancreatitis [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: October 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linagliptin 5mg
given once daily over 28 days
Drug: Placebo
Placebo matching Glimepiride
Drug: Linagliptin
given once daily for 28 days
Active Comparator: Glimepiride
given once daily in 1mg dosis over 7 days, following a titration step to 2mg and application for 21 days
Drug: Placebo
Placebo matching Linagliptin
Drug: Glimepiride
1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days)
Placebo Comparator: Placebo
given once daily over 28 days
Drug: Placebo
Placebo matching Linagliptin
Drug: Placebo
Placebo matching Glimepiride

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703286

Locations
Germany
1218.105.001 Boehringer Ingelheim Investigational Site
Neuss, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01703286     History of Changes
Other Study ID Numbers: 1218.105, 2012-003317-33
Study First Received: October 1, 2012
Last Updated: January 22, 2014
Health Authority: Germany: Federal Ministry of Food, Agriculture and Consumer Protection

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Linagliptin
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014