Men or women diagnosed with type 2 diabetes and treated with diet alone or on treatment with a single oral anti diabetic agent or low doses of two agents, and with diabetic dyslipidaemia
Conditions
Interventions
Product Name: Tesaglitazar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tesaglitazar
CAS Number: 251565-85-2
Current Sponsor code: AZ242
Concentration unit: mg milligram(s)
Concentrati
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 visit 1 2.Men or women who are 18 years of age or older at time of consenting upon visit 1 3.Female patients post menopausal, hysterectomized or if of childbearing potential using a reliable method of birth control. 4.Diagnosed with type 2 diabetes 5.Treated with diet alone or treatment with a single oral anti-diabetic agent or low doses of two oral anti-diabetic agents. All anti-diabetic medications are to be discontinued at visit 1. Treatment with lipid lowering medication, including statins, must be discontinued at visit 1. Inclusion criteria at placebo run-in (visit 2, lab values from visit 1): 6.For patients 0.8 ng/mL, 0.26 nmol/L 7.HbA1c equal to or over 7 % for patients not on any anti-diabetic drug for 12 weeks prior to visit 1. No lower HbA1c-limit for patients treated with oral anti-diabetic drug(s) within 12 weeks prior to visit 1. 8.HbA1c equal to or lower then 10% 9.FPG equal to or lower then 13.3 mmol/L, 240 mg/dL 10.HDL-C equal to or lower then 40 mg/dL (equal to or lower then 1.03 mmol/L) for males and equal to or lower then 50 mg/dL (1.29 mmol/L) for females Inclusion criteria at randomisation (visit 5, lab values from visit 3 and 4): 11.HbA1c equal to or higher then 7 % for patients not on any anti-diabetic drug for 12 weeks prior to visit 1. No lower HbA1c-limit for patients treated with oral anti-diabetic drug(s) within 12 weeks prior to visit 1. 12.HbA1c equal to or lower then 10% 13.Mean FPG from two measurements (lab values from visit 3 and 4) £13.3 mmol/L, 240 mg/dL 14.HDL-C equal to or lower then 40 mg/dL (1.03 mmol/L) for males and equal to or lower then 50 mg/dL (1.29 mmol/L) for females Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 ischaemic attack, cerebrovascular accident, myocardial or peripheral vascular disease, revascularization or angioplasty within 24 weeks prior to visit 1 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 hypertriglyceridaemia induced pancreatitis 7.Pregnant or breastfeeding patients 8.Suspicion that the patient is infected according to world health organisation (WHO) risk categories 2 to 4 (See Appendix H) 9.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) 10.Treatment with combination therapy (i.e. two anti diabetic agents, except low doses of two agents, see Section 3.7) within 12 weeks prior to visit 1 11.Treatment with a thiazolidinedione within 4 weeks prior to visit 1 12.Treatment with fibrates, within 4 weeks prior to visit 1 13.Treatment with glucocorticoids (equivalent to oral prednisolon >10 mg per day), within 4 weeks prior to visit 1 14.Treatment with probenecid that cannot be stopped at visit 1 15.History of hypersensitivity or intolerance to any PPAR agonist 16.Pre-existing medical conditions that is contraindicated for the use of fenofibrate 17.Intolerance to metformin at any time in the past, or pre-existing medical conditions that is contraindicated for the use of metformin 18.Intolerance to an HMG-CoA reductase inhibitor (statin) at any time in the past, or pre-existing medical conditions that is contraindicated for the use of statins 19.History of drug-induced myopathy or drug-induced CK elevation 20.History of drug-induced liver enzyme elevations 21.History of drug-induced neutropenia 22.History of alcohol or drug abuse within the last 5 years 23.Other serious or unstable medical or psychological condition identified in the patient’s medical history that, in the judgement of the investigator, would compromise the patient’s safety or successful participation in the Clinical Study 24.Receiving any investigational product in other clinical studies within 12 weeks prior to visit 1 25.Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational site) 26.Previous enrolment or randomisation of treatment in the present study Exclusion criteria at run-in (visit 2, lab values from visit 1) 27.Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgement of the investigator would compromise the patient’s safety or successful participation in the study 28.NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F. 29.Fasting TG >7.0 mmol/L, 620 mg/dL 30.Hb 2.5 times the upper limit of normal 33.Total bilirubin above the upper limit of normal unless exclusively caused by Gilbert’s syndrome 34.Creatinine above the upper limit of normal 35.CK >3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The two primary objectives of this study are to assess whether tesaglitazar is superior to metformin and non-inferior to metformin combined with fenofibrate in increasing high density lipoprotein-cholesterol (HDL-C) in patients with type 2 diabetes and low HDL-C on a fixed background therapy with a statin, as determined by the change in HDL-C from baseline (visit 5) to the end of the 24-week randomised treatment period (visit 14). ;Secondary Objective: To compare the effects of tesaglitazar versus metformin and versus metformin combined with fenofibrate in improving lipids and lipoproteins in patients with type 2 diabetes and low HDL-C on a fixed background therapy with a statin after a 24-week randomised treatment period by evaluation of: To compare the effects of tesaglitazar versus metformin and versus metformin combined with fenofibrate on risk markers for cardiovascular disease To compare the effects of tesaglitazar versus metformin and versus metformin combined with fenofibrate on central obesity (waist/hip ratio) To evaluate the pharmacokinetics of tesaglitazar To evaluate the safety and tolerability of tesaglitazar ;Primary end point(s): Primary outcome variable: -Change in HDL-C from baseline (visit 5) to the end of the randomised treatment period (visit 14) | — |
Countries
Czech Republic, Finland, Germany, Hungary
Outcome results
None listed