E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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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 |
The primary objective is to investigate the effect of Pioglitazone in comparison to Metformin and the combination of both on MMP9 in patients with diabetes mellitus type 2 treated with insulin. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are • Circadian (7 point) blood glucose profile on 2 days in the week before V2.2, V4, and V6.2 • 24h blood pressure profile • IMT • Kidney function (24-hour urine, PGFα, albumin, creatinine, C/A-quotient) • NT-proBNP • HOMA S • Lipid profile (total cholesterol, LDL, HDL, triglycerides) • Metabolic markers (HbA1c, glucose, insulin, intact proinsulin, C-peptide, adiponectin, HMW adiponectin) • Inflammatory markers (hsCRP, fibrinogen, E-selectin, NFκB, PAI-1, nitrotyrosine) • Insulin consumption • Endothelial function measured by Laser-Doppler-Flowmetrie (O2C) • Laboratory safety variables including ALAT, ASAT,G-GT, GFR (Cockroft-Gault formula), AP, leucocytes, erythrocytes, haemoglobin, thrombocytes, CK, creatinine, capillary blood glucose, potassium • Side effects including body weight and ECG |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study to evaluate the changes in the body composition (weight, fat%, fat mass, fat free mass, muscle mass, total body water, BMI, visceral fat rating, bone mass, ratio intercellular and intracellular water) via bioelectrical impendance analysis. The generated data will be another secondary objective of the trial. This sub-study will only be performed at the site of Dr. Kress in Landau. It is planned to investigate about 20 patients and the results will be analyzed in a descriptive way only. The sub-study has been integrated in the clinical trial protocol version 8.0, 25-Feb-2009. |
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E.3 | Principal inclusion criteria |
1. Diabetes mellitus type 2 2. HbA1c >= 6.5% <= 8.5% 3. Treatment with the following insulins with or without OAD Therapy since 3 months: a. Long acting basal insulin analogs, b. NPH insulin, c. Combination insulin with 1-2 daily doses; except intensified insulin therapies 4. Age 30 – 75 years 5. BMI >= 25 6. Written informed consent
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E.4 | Principal exclusion criteria |
1. History of type 1 diabetes mellitus 2. Uncontrolled hypertension (systolic blood pressure >160mmHg and/or diastolic blood pressure >95mmHg), change of antihypertensive treatment within the last 2 weeks 3. Acute infections 4. NSAIDs (incl. low dose ASA) or Cox-2-inhibitors if therapy initiated within the last 4 weeks 5. Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structure 6. History of severe or multiple allergies 7. Treatment with any other investigational drug within 4 weeks before trial entry 8. History of drug or alcohol abuse in the past 5 years 9. A history of significant cardiovascular (NYHA stage I - IV; determined by anamnesis and clinical status), respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 2.5 times the upper limit of the normal reference range), renal (serum creatinine > 1.2 mg/dL in women and > 1.5 mg/dL in men, GFR < 60 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or haematological disease as judged by the investigator 10. History of macular oedema 11. State after kidney transplantation 12. Serum potassium > 5.5 mmol/L 13. History of primary hyperaldosteronism 14. Pregnancy or breast feeding 15. Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomised partner 16. Treatment with thiazolidinediones within the past 3 months 17. Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous year 18. Any elective surgery during study participation 19. If statin therapy applicable: Change of medication within the last 4 weeks 20. Pre-treatment with gemfibrozil within the last 12 weeks 21. Pre-treatment with rifampicin within the last 12 weeks 22. Have had more than one unexplained episode of severe hypoglycaemia (defined as requiring assistance of another person due to disabling hypoglycaemia) within 6 months prior to screening visit 23. History of dehydration, precoma diabeticum or shock or diabetic ketoacidosis within the past year prior to screening visit 24. Acute or scheduled investigation with iodine containing radiopaque material 25. Uncontrolled unstable angina pectoris 26. Medical history of acute and clinically relevant pericarditis, myocarditis, endocarditis, recent pulmonary embolism, hemodynamic relevant aortic stenosis, aortic aneurysm 27. Postmenopausal woman with present osteoporosis
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variable is the change of MMP9 after 6 months of treatment as compared to baseline.
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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 | Yes |
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 | 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) | Yes |
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 | 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) | 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 | 20 |
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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Last visit of the last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |