Type II Diabetes Mellitus MedDRA version: 7 Level: LLT Classification code 10045242
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of a written informed consent at Visit 1 2.Men or women who are =18 years of age at time of consenting upon Visit 1 3.Female patients who are post menopausal, have undergone a hysterectomy, or if of childbearing potential, are using an effective method of birth control Post menopausal patients are defined as patients with: -Natural or induced menopause with last menstruation >1 year ago, or -Bilateral oophorectomy A highly effective method of birth control is defined as combination oral contraceptive, implant, long term injectable contraceptive, intrauterine device or tubal ligation. However, female patients using oestrogen containing hormonal anti conception methods (oral, transdermal, vaginal ring or combination injectables) must agree to use an additional anti conception method. 4.Diagnosed with type 2 diabetes. For patients 0.8 ng/mL, 0.27 nmol/L. 5.FPG =13.3 mmol/L, 240 mg/dL 6.Treated with metformin alone for the last three months or more, or treated with metformin for the last three months plus one additional oral anti-diabetic agent in low dose (maximal daily dose of metformin 2.7 g/day). The additional anti-diabetic medication is required to be discontinued at the enrolment visit. The low doses of additional anti-diabetic medication are defined as a maximal daily dose of sulphonylurea comparable to glibenclamide/glyburide 5 mg (corresponding to 3.5 mg of Swedish microcristal form of glibenclamide), meglitinide comparable to repaglinide 1.5 mg or alpha-glucosidase inhibitors comparable to acarbose 150 mg. Inclusion criteria at randomisation (Visit 2): 7.HbA1c =8.5 % 8.Mean FPG of two measurements (values from Visit 1 and 2, measured capillary) =11.7 mmol/L, 210 mg/dL 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 ischemic attack, cerebrovascular accident, myocardial or peripheral vascular disease revascularization or angioplasty within 24 weeks prior to Visit 1 3.Pre-existing chronic heart failure (NYHA class I-IV) 4.High blood pressure (mean systolic blood pressure =160 mm Hg, mean diastolic blood pressure =90 mm Hg after 3 repeated measurements) with or without anti-hypertensive treatment. 5.History of thyroid ophthalmopathy 6.History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma 7.History of blood lipid induced eruptive xanthomas, or hypertriglyceridaemia induced pancreatitis 8.Suspected untreated proliferative diabetic retinopathy, as judged by the investigator 9.Other conditions predisposing for development of lactatic acidosis, eg, chronic obstructive pulmonary disease (COPD) 10.Pregnant or breastfeeding patients 11.Suspicion that the patient is infected according to World Health Organisation (WHO) risk categories 2 to 4 (See Appendix C) 12.Treatment of type 2 diabetes with combination therapy (ie, additional antidiabetic agents, except low dose of 1 oral antidiabetic agent, see Section 3.4.5) 13.Treatment with chronic insulin, within 24 weeks prior to Visit 1 (however, 1 temporary period of daily insulin injections no longer than 7 days is allowed) 14.Treatment with a thiazolidinedione (eg, pioglitazone, rosiglitazone) within 4 weeks prior to Visit 1 15.Treatment with fibrates, within 4 weeks prior to Visit 1 16.Treatment with glucocorticoids (equivalent to oral prednisolone >10 mg per day), within 4 weeks prior to Visit 1 17.Treatment with probenecid that can not be stopped at Visit 1 18.History of hypersensitivity or intolerance to any PPAR agonist 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 patients’ medical history that, in the judgement of the investigator, would compromise the patients’ safety or successful participation in the Clinical Study 24.Receiving any investigational product during the last 12 weeks prior to Visit 1 25.Previous enrolment in this study 26.Any clinically significant abnormality identified on physical examinations, laboratory tests or ECG, which in the judgement of the investigator would compromise the patients’ safety or successful participation in the Clinical Study 27.Other serious or unstable medical or psychological condition identified in the patients’ medical history that, in the judgement of the investigator, would compromise the patients’ safety or successful participation in the Clinical Study 28.Fasting TG >7.0 mmol/L, 620 mg/dL 29.Hb 2.5 times the upper limit of normal 32.Total bilirubin above the upper limit of normal unless exclusively caused by Gilbert’s syndrome 33.Creatinine > 135 µmol/L for men or > 110 µmol/L for women 34.Calculated creatinine clearance 3 times the upper limit of normal 36.Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): This study has no end points, however the primary variable is: AUCss of metformin during the last day-time 12-h dosing interval after 12-week treatment with metformin and tesaglitazar as compared to treatment with metformin and placebo in patients with type 2 diabetes with CrCL>70 mL/min or CrCL=70 to =50mL/min.;Main Objective: To compare the effect of 1 mg tesaglitazar once daily versus placebo once daily given as add?on therapy to metformin on the steady state exposure (AUCss) of metformin in patients with type 2 diabetes with a serum creatinine within normal range and having CrCL>70 mL/min or CrCL=70 to =50mL/min, by assessment after a 12-week randomized treatment period.;Secondary Objective: 1.Compare effect of 1 mg tesaglitazar once daily versus placebo once daily given as addon therapy to metformin on the pharmacokinetics of metformin in patients with type 2 diabetes with a serum creatinine within normal range and having CrCL>70 mL/min or CrCL=70 to =50mL/min, by assessment of Css,max, tss,max, Css,min and CLR of metfomin, after a 12-week randomized treatment period. 2.Compare the effects of 1 mg tesaglitazar once daily versus placebo once daily given as add-on therapy to metformin on GFR, in patients with type 2 diabetes with a serum creatinine within normal range and having CrCL>70 mL/min or CrCL=70 to =50mL/min, by assessment of plasma clearance of 51Cr-EDTA, and endogenous CrCL after a 12-week randomized treatment period. 3.Evaluate the safety and tolerability of 1 mg tesaglitazar once daily given as add-on therapy to metformin, by assessment of AEs, laboratory values, ECG, pulse, blood pressure, hypoglycaemic events, body weight and physical examination. | — |
Countries
Sweden
Outcome results
None listed