E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus and sublinical heart failure |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 investigate whether 18 weeks treatment of liraglutide (Victoza) will improve subclinical heart failure (measured with echocardiogram and tissue doppler) in type 2 diabetic subjects versus glimepiride both in combination with metformin
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E.2.2 | Secondary objectives of the trial |
To investigate the tolaribility of the 18 weeks use of Victoza in type 2 diabetic subjects with subclinical heart failure. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Type 2 diabetes. 2 Heart Failure, visualized with echocardiography, one of the following (2.1, 2.2 or 2.3). 2.1 Ejection Fraction ≤ 50%. 2.2 Decreased systolic velocity (four chamber view) where two, out of four segments (Septum, Lateral, Inferior and Anterior Wall) has a relative decrease in velocity of 20% compared to a normal population. 2.3 Evidence of diastolic dysfunction as shown by abnormal left ventricular relaxation, filling, diastolic distensibility or stiffness. An E/E’ ratio (ratio of early diastolic velocities of mitral inflow derived Doppler imaging and myocardial movement derived by tissue Doppler imaging) >15 is considered diagnostic of diastolic dysfunction and an E/E′ ratio < 8 as diagnostic of the absence of diastolic heart failure. An increased left atrial size (>49 ml/ m2) and an increased left ventricular mass (>122 g/m2 in women and >149 g/m2 in men) are considered sufficient evidence of diastolic dysfunction when the E/E′ ratio is inconclusive. 3 HbA1c (accordingly to IFCC) 60 mmol/mol – 95 mmol/mol. 4 If antihypertensive treatment, the medication has to be stable, no change, for the last 1 month. 5 Male and female subjects, 18-70 years of age. 6 Signed informed consent form.
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E.4 | Principal exclusion criteria |
1. Type 1 diabetes (autoantibody positive). 2. Any history of receiving GLP-1 analogues or dipeptidyl peptidase inhibitors (DPP-IV inhibitor) or glimeperid. 3. Previous treatment with glitazones within 6 months. 4. Previous treatment with other sulphonylurea within 3 months. 5. Previous treatment with insulin (any regimen) within 1 month.. 6. Known severe heart failure, classified as NYHA 3-4. 7. Significant ischemic heart disease (defined as angina-limited exercise or unstable angina); documented acute myocardial infarction (MI) within the previous 8 weeks. 8. Active myocarditis; malfunctioning artificial heart valve. 9. Atria fibrillation or flutter 10. History of ventricular tachycardia within 3 months before study entry; second- or third-degree atrioventricular block. 11. Implanted pacemaker. 12. Supine systolic blood pressure <85 mm Hg or >200 mm Hg? 13. Primary renal impairment (creatinine clearance < 30 ml/min), or creatinine clearance < 60 ml/min if treated with metformin. 14. Uncorrected hypokalemia or hyperkalemia (potassium <3.5 mmol/l or >5.5 mmol/l). 15. Significant anemia (Hb < 90 g/l) 16. Treatment with another investigational agent within 30 days before study entry, judged by the investigator. 17. Severe gastrointestinal disease, including gastroparesis. As judged by the investigator. 18. Body mass index (BMI) > 40 kg/m2. 19. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years. Patients with intraepithelial squamous cell carcinoma of the skin treated with topical 5FU and subjects with basal cell skin cancer are allowed to enter the trial. 20. Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice). 21. Current drug and alcohol abuse. 22. History of acute or chronic pancreatitis 23. Subjects considered by the investigator to be unsuitable for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Subjects achieving an absolute increase in left ventricle longitudinal function and/or functional reserve during rest and/or after exercise of 0.7 cm/s, i.e., ΔE’ [1-(1/E’base)] or ΔS’ [1-(1/S’base)] after 18 weeks of liraglutide + metformin, compared with glimepiride + metformin, using tissue Doppler echocardiography. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |