E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
To establish, whether liraglutide improves the glucagon concentration under hypoglycaemic conditions in patients with type 2 diabetes |
|
E.2.2 | Secondary objectives of the trial |
To establish, whether liraglutide treatment
1) increases the amplitude and mass of pulsatile glucagon secretion in response to hypoglycaemia
2) reduces the amplitude and mass of pulsatile glucagon secretion in response to oral glucose
3) increases the amplitude and mass of pulsatile insulin secretion in response to oral glucose
4) improves the interaction between pulsatile insulin and glucagon secretion
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Type 2 diabetes mellitus (at least 6 months) based on the disease diagnostic criteria WHO) classification
• In case of existing therapy with sulfonlyurea or DPP 4–inhibitors agreement to pause the medication 4 weeks before visit 3 takes place and during the study.
• Men or women from 18 to 70 years, inclusive
|
|
E.4 | Principal exclusion criteria |
• Any contraindications, known allergy / hypersensitivity to liraglutide or another GLP-1 analogue or excipients contained in these products.
• Participation in an interventional medical, surgical or pharmaceutical study within the last three months prior to entry into the study
• Any other condition that may preclude the patient from following and completing the protocol
• Patients with type 1 diabetes mellitus
• Women of child-bearing age, who are pregnant, plan a pregnancy or do not use a sufficient method of contraception (sterilisation, intrauterine hormone application, oral contraceptives, sexual abstinence or vasectomised partners).
• Any evidence that the patient will probably not comply with the trial protocol (e.g. lack of willingness to cooperate)
• Pharmacotherapy with digoxin, lisinopril, warfarin, insulin, GLP-1 analogues
• Patients with moderate and severe renal impairment (creatinine clearance < 59 ml/min)
• Impaired liver function (GOT and/or GPT 3x ULN)
• History of benign/malign thyroid tumours
• History of chronic pancreatitis/idiopathic acute pancreatitis
• Cardiac insufficiency NYHA stage I – IV
• Manifest CHD; history of myocardial infarction
• Chronic inflammatory enteropathy
• Diabetic gastroparesis
• Patients with known haemoglobinopathy or chronic anaemia (Hb < 10 mg/dl)
• Patients on systemic glucocorticoid treatment (except topic or inhalative preparations) within the last 3 months prior to screening
• History of thrombosis/embolism, coagulation disorders
• Alcohol abuse
• Oncologic disease (except basal cell Ca and squamous cell carcinoma of the skin)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Concentrations of insulin, C-peptide and glucagon
* before and after treatment with liraglutide or placebo
* between euglycaemic and hypoglycaemic periods within the clamp experiment
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before and after 56 days treatment with study drug/placebo |
|
E.5.2 | Secondary end point(s) |
1. Cortisol levels in the course of the clamp experiment
2. Growth hormone (GH) levels in the course of the clamp experiment
3. Adrenaline levels in the course of the clamp experiment
4. Noradrenaline levels in the course of the clamp experiment
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before and after 56 days treatment with study drug/placebo |
|
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 | No |
E.8.1.6 | Cross over | Yes |
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
|
It is intendend to end the trial with the last visit of the last patient.
|
|
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 |