Official Title: “A 24-Week Randomised, Double-Blind, Parallel-Group, Multi-Centre, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Tesaglitazar Therapy When Added to the Therapy of Patients With Type 2 Diabetes Poorly Controlled on Sulphonylurea Alone”

This is a 24-week randomized double-blind, parallel-group, multi-center, placebo-controlled study of tesaglitazar (0.5 mg and 1 mg) given as add-on therapy to sulphonylurea in patients with type 2 diabetes, not adequately controlled on optimized sulphonylurea treatment and on diet/lifestyle advice during the titration and run-in period. The study comprises a 2-week enrollment period, 6 week placebo metformin titration period, 2-week single-blind run-in period, followed by a 24-week double blind treatment period and a 3-week follow-up period

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: Tesaglitazar 0.5 or 1 mg
• Drug: Glibenclamide 2.5, 5, 10 or 15 mg

Primary Measures

• Absolute change from baseline to end of randomized treatment period in glycosylated hemoglobin A1c (HbA1c)

Secondary Measures

• Changes in the following variables from baseline to the end of the randomized treatment period:
• • The change in fasting plasma glucose (FPG), insulin, proinsulin and C-peptide
• • Insulin sensitivity by assessment of change in the calculated variable homeostasis assessment model
• • Lipid parameters (triglyceride [TG], total cholesterol, high-density lipoprotein cholesterol [HDL C], non-HDL C, low-density lipoprotein cholesterol [LDL C], apolipoproteins [Apo] A-I, Apo B, Apo CIII, free fatty acids, lipoprotein particle size and c
• • C-reactive protein, LDL C/HDL C ratio and Apo B/Apo A-I ratio
• • FPG, homeostasis assessment model, insulin, proinsulin, C-peptide
• • Tumor necrosis factor-alpha, intracellular adhesion molecule-1
• • Fibrinogen
• • Urinary albumin excretion
• • Waist/hip ratio
• • Responder analyses for HbA1c, FPG, TG, HDL C, total cholesterol, non HDL C and LDL C according to pre-specified values
• • Proportion of patients reaching pre-specified target levels for HbA1c, FPG, TG, HDL C, non-HDL C and LDL C
• • Pharmacokinetics of tesaglitazar
• • Safety and tolerability of tesaglitazar by assessment of adverse events, laboratory values, electrocardiogram, pulse, blood pressure, hypoglycemic events, body weight, cardiac evaluation, and physical examination

Inclusion Criteria:

• Provision of a written informed consent
• Female patients: postmenopausal, hysterectomized, or if of childbearing potential, using a reliable method of birth control
• Diagnosed with type 2 diabetes
• Treated with diet alone or treatment with a single oral antidiabetic agent or low doses of two oral antidiabetic agents

Exclusion Criteria:

• Type 1 diabetes
• New York Heart Association heart failure Class III or IV
• Treatment with chronic insulin
• History of hypersensitivity or intolerance to any peroxisome proliferator-activated receptor agonist (like Actos or Avandia), fenofibrate, metformin or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)
• History of drug-induced myopathy or drug-induced creatine kinase elevation, liver enzyme elevations, neutropenia (low white blood cells)
• Creatinine levels above twice the normal range
• Creatine kinase above 3 times the upper limit of normal
• Received any investigational product in other clinical studies within 12 weeks
• Any clinically significant abnormality identified on physical examination, laboratory tests or electrocardiogram, which in the judgment of the investigator would compromise the patient's safety or successful participation in the clinical study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: AstraZeneca

Overall Clinical Trial Officials and Contacts

AstraZeneca Galida Medical Science Director, MD Study Director AstraZeneca  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00251940

Study ID Number: D6160C00032

ClinicalTrials.gov Identifier: NCT00251940

Health Authority: United Kingdom: Department of Health