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 | 7 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
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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 of this study is to determine the efficacy of tesaglitazar given as monotherapy as compared to placebo in patients with type 2 diabetes in improving whole body insulin sensitivity by assessing the M value during high (80mU/m2/min) insulin level euglycemic hyperinsulinemic clamp. |
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E.2.2 | Secondary objectives of the trial |
1To determine the efficacy of tesaglitazar given as monotherapy as compared to metformin in type 2 diabetic patients in improving whole body insulin sensitivity 2To determine the efficacy of tesaglitazar given as monotherapy as compared to placebo/metformin in type 2 diabetic patients in improving hepatic and peripheral insulin sensitivity 3To assess the effects of tesaglitazar given as monotherapy as compared to placebo/metformin in type 2 diabetic patients on: basal hepatic glucose output;the plasma profile of glucose, insulin and lipids after a mixed meal;calculated insulin secretion;energy expenditure and substrate metabolism by indirect calorimetry;body composition using DXA-scan, abdominal fat distribution using magnetic resonance imaging, liver fat and muscle fat content using magnetic resonance spectroscopy;laboratory efficacy variables 4Exploratory assess the plasma levels of amino acids 5To determine the safety and tolerability of tesaglitazar in type 2 diabetic patients |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion criteria at enrolment (visit 1):
1. Provision of a written informed consent at the enrolment visit 2. Male or female, 30–70 years old. Females must be post menopausal or hysterectomized. Post menopausal patients are defined as patients with: -Natural or induced menopaus with last menstruation more than 12 months ago, or -Bilateral oophorectomy 3. Diagnosed with type 2 diabetes >12 weeks ago 4. Treated with diet alone or treatment with a single oral agent or low doses of two agents. All antidiabetic medications are required to be discontinued at enrolment visit.
Inclusion criteria at placebo run-in (visit 2, lab values from visit 1): 5. HbA1c >6.5% for patients not on any anti-diabetic drug for 12 weeks prior to visit 1 6. HbA1c <8,5% if previously drug-naïve and <7,5% if previously treated with a single oral agent or low doses of two agents 7. FPG <13.3 mmol/L, 240 mg/dL
Inclusion criteria at randomization (visit 5, lab values from visit 3 and 4): 8. HbA1c >6.5 % for patients not on any anti-diabetic drug for 12 weeks prior to visit 1 (lab value from visit 4) 9. HbA1c <8,5% if previously drug-naïve and <7,5% if previously treated with a single oral agent or low doses of two agents (lab value from visit 4) 10. Mean FPG from two measurements (lab values from visit 3 and 4) FPG <13.3 mmol/L, 240 mg/dL.
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E.4 | Principal exclusion criteria |
Exclusion criteria at enrolment (visit 1): 1. Type 1 diabetes, history of diabetic ketoacidosis, or corticosteroid-induced type 2 diabetes. 2. Active arterial disease such as unstable angina, myocardial infarction, transient ischemic attack (TIA), cerebrovascular accident (CVA), myocardial or peripheral vascular disease (PVD) revascularization or angioplasty within 24 weeks prior to enrolment visit 3. NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F. 4. History of thyroid ophthalmopathy. 5. History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma. 6. History of blood lipid induced eruptive xanthomas or hypertriglyceridemia induced pancreatitis. 7. Suspicion that the patient is infected according to world health organisation (WHO) risk categories 2 to 4 (see Appendix G). 8. Treatment with chronic insulin, within 24 weeks prior to visit 1 (however, one temporary period of daily insulin injections no longer than 7 days is allowed) 9. Treatment with combination therapy (i.e. two anti diabetic agents, except low doses of two agents, see Section 3.4.5) within 12 weeks prior to visit 1 10. Treatment with a PPARgamma or PPARalpha/gamma agonists within 24 weeks prior to visit 1 11. Treatment with fibrates (PPARalpha agonist), within 4 weeks prior to visit 1 12. Treatment with systemic corticosteroids , within 4 weeks prior to visit 1. 13. Treatment with probenecid that cannot be stopped at visit 1 14. History of hypersensitivity or intolerance to any PPAR agonist 15. Intolerance to metformin at any time in the past or preexisting medical conditions that is contraindicated for the use of metformin. 16. History of drug-induced myopathy or drug-induced CK elevation. 17. History of drug-induced liver enzyme elevations. 18. History of drug-induced neutropenia. 19. History of alcohol or drug abuse within the last 5 years. 20. Other serious or unstable medical or psychological condition identified on medical history that, in the judgement of the investigator, would compromise the patients’ safety or successful participation in the study. 21. Receiving any investigational product within 12 weeks (90 days) prior to visit 1. 22. Previous enrolment in this study. 23. Body weight >120 kg
Exclusion criteria at placebo run-in (visit 2, lab values from visit 1) 24. Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgement of the investigator would compromise the patients’ safety or successful participation in the study. 25. NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F. 26. Fasting TG >7.0 mmol/L, 620 mg/dL. 27. Hb <90 g/L, 9 g/dL. 28. Absolute neutrophile count (ANC) <1.0x 109/L. 29. Any of ALT, AST or ALP >2.5 times the upper limit of normal. 30. Total bilirubin above the upper limit of normal unless exclusively caused by Gilbert’s syndrome. 31. Creatinine > the upper limit of normal. 32. CK >3 times the upper limit of normal.
Exclusion criteria at randomization (visit 5, lab values from visit 3 and4) 33. Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgement of the investigator would compromise the patients’ safety or successful participation in the study. 34. NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F. 35. Other serious or unstable medical or psychological condition identified on medical history that, in the judgement of the investigator, would compromise the patients’ safety or successful participation in the study. 36. High blood pressure (mean diastolic BP >120 mm Hg) or malignant hypertension. 37. Hb <90 g/L, 9 g/dL. 38. ANC <1.0x 109/L. 39. Any of ALT, AST or ALP >2.5 times the upper limit of normal. 40. Total bilirubin above the upper limit of normal unless exclusively caused by Gilbert’s syndrome. 41. Creatinine > the upper limit of normal. 42. CK >3 times the upper limit of normal.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the M value during the last 40 minutes (140-180 minutes) of the second clamp step adjusted for lean body mass (mg/min/kg). |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | 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 | 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 | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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End of study is defined as date of database lock. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 |