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)

NCT01703286 | Completed Phase 1 Results

• 2 other identifiers: 1218.1052012-003317-33
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Change From Baseline in Flow Mediated Vasodilation (FMD) 2 h Post Meal on Day 28

  baseline and day 28 for each treatment arm

• Change From Baseline in 2 Hours Post Meal Endothelial Independent Vasodilation (EIDV) on Day 28

  baseline and day 28 for each treatment arm

• Number of Patients With Adverse Events

  up to 20 weeks

Study Arms (3)

Linagliptin 5mg

EXPERIMENTAL

given once daily over 28 days

Drug: Placebo; Drug: Linagliptin

Glimepiride

ACTIVE COMPARATOR

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

Drug: Placebo; Drug: Glimepiride

Placebo

PLACEBO COMPARATOR

given once daily over 28 days

Drug: Placebo

Interventions

Placebo DRUG

Placebo matching Glimepiride

Linagliptin 5mg

Linagliptin DRUG

given once daily for 28 days

Linagliptin 5mg

Glimepiride DRUG

1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days)

Glimepiride

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Treatment with any glucose-lowering drug except for metformin within prior 3 months.
• Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance.
• Any evidence of a clinically relevant acute concomitant disease
• History of cardiovascular disease (e.g. coronary artery disease history of acute myocard infarction or stroke, peripheral vascular disease).
• History of major diabetic complications (e.g. nephropathy, retinopathy)
• 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).
• Surgery of the gastrointestinal tract (except appendectomy).
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders.
• History of relevant orthostatic hypotension, fainting spells or blackouts.
• Chronic or relevant acute infections.
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).
• 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.
• Participation in another trial with an investigational drug within one month prior to administration or during the trial.
• Smoker (\>= 1 cigarettes or \>= 1 cigars or \>= 1 pipes/day).
• Alcohol abuse (more than 60 g/day).

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

1218.105.001 Boehringer Ingelheim Investigational Site

Neuss, Germany

Location

Related Publications (1)

• 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.

  PMID: 28109295 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Linagliptin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2012
• First Posted: October 10, 2012
• Study Start: October 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 19, 2015
• Results First Posted: January 19, 2015

Record last verified: 2015-01

Locations

DE (1)