E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes mellitus Type 2 |
Diabetes mellitus Typ 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Diabetes Type 2 |
Typ 2 Diabetes, Zuckerkrankheit |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to investigate the impact of a 12 week linagliptin treatment on endothelial function in patients with early type 2 diabetes. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to investigate the effect of a 12 week linagliptin treatment on:
- arginine bioavailability ratios (global arginine bioavailability ratio and arginine to ornithine ratio)
- biochemical markers of endothelial function (sVCAM-1, sICAM-1, vWF)
- the AUC of glucose, insulin and free fatty acids during the meal tolerance test |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 40-75
- Early diabetes (postchallenge diabetes (2h glucose >200 mg/dl or type 2 diabetes treated with diet only or on a stable dose of metformin monotherapy)
- Coronary atherosclerosis (diagnosed via coronary angiography or coronary computer tomography) |
|
E.4 | Principal exclusion criteria |
- Acute coronary syndrome or cerebrovascular event within the previous 4 weeks
-BMI > 35 kg/m2
- Serum creatinine > 2.5 mg/dl
- AST/ALT > 3x upper limit of normal
- HbA1c >9.0% (>75 mmol/mol)
- Heart failure > NYHA class II
- Uncontrolled hypertension (blood pressure > 165 / 100 mmHg)
- Treatment with orally administered steroids
- New onset statin or ACE-inhibitor within the previous 6 weeks
- Known Malignancy
- Pregnancy or breast feeding women. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Changes in endothelial function (assessed by flow mediated dilatation – FMD) from baseline to 12 week. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Changes from Baseline to week 12 in:
- the arginine bioavailability ratios (global arginine bioavailability ratio and arginine to ornithine ratio)
- in biochemical markers of endothelial function (sVCAM-1, sICAM-1, vWF)
- in the AUC of glucose, insulin and free fatty acids during the meal tolerance test |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |