Type 2 diabetes MedDRA version: 7 Level: LLT Classification code 10045242
Conditions
Interventions
Product Name: Tesaglitazar
Product Code: AZ242
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tesaglitazar
CAS Number: 251565-85-2
Other descriptive name: Az242
Concentration unit: mg m
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
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 6.5 % for patients not on any anti-diabetic drug for 12 weeks prior to visit 1 (lab value from visit 4) 9. HbA1c =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 Cl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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;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). | — |
Countries
Italy, United Kingdom
Outcome results
None listed