GALLANT 8 Tesaglitazar Add-on to Metformin

Condition(s) targeted: Type 2 Diabetes

Intervention: Tesaglitazar (Drug); Metformin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
AstraZeneca Galida Medical Science Director, MD, Study Director, Affiliation: AstraZeneca

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 metformin in patients with type 2 diabetes, not adequately controlled on optimized metformin 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

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 Metformin Alone

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

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

Secondary outcome:

Changes in the following variables from baseline to the end of the randomized treatment period:

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

Minimum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Provision of a written informed consent

- Men or women who are >=18 years of age

- 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

Research Site, Coquitlam, British Columbia, Canada

Research Site, Pistoia, Italy

Research Site, Pescara, Italy

Research Site, Liverpool, United Kingdom

Research Site, Ängelholm, Sweden

Research Site, Chippenham, United Kingdom

Research Site, Harrow, United Kingdom

Research Site, Scandiano, Italy

Research Site, Melbourne, Australia

Research Site, Hamburg, Germany

Research Site, Milano, Italy

Research Site, Vantaa, Finland

Research Site, Atherstone, United Kingdom

Research Site, Monteccio Emilia, Italy

Research Site, Napoli, Italy

Research Site, Hyderabad, India

Research Site, Leeds, United Kingdom

Research Site, Hämeenlinna, Finland

Research Site, Chieri, Italy

Research Site, Cairns, Australia

Research Site, Messina, Italy

Research Site, Perugia, Italy

Research Site, Piacenza, Italy

Research Site, Kuala Lumpur, Malaysia

Research Site, Adelaide, Australia

Research Site, Oulu, Finland

Research Site, Malmö, Sweden

Research Site, Reggio Emilia, Italy

Research Site, Rotenburg/Fulda, Germany

Research Site, Marsala, Italy

Research Site, New Delhi, India

Research Site, Kouvola, Finland

Research Site, Mölndal, Sweden

Research Site, Edinburgh, United Kingdom

Research Site, Göteborg, Sweden

Research Site, Singapore, Singapore

Research Site, Wrexham, United Kingdom

Research Site, Barry, United Kingdom

Research Site, Borås, Sweden

Research Site, Glasgow, United Kingdom

Research Site, Aldershot, United Kingdom

Research Site, Sydney, Australia

Research Site, Cardiff, United Kingdom

Research Site, Höganäs, Sweden

Research Site, Chiavari (GE), Italy

Research Site, Uppsala, Sweden

Research Site, Kuopio, Finland

Research Site, Kungsör, Sweden

Research Site, Hastings, United Kingdom

Research Site, Swindon, United Kingdom

Research Site, Stenungsund, Sweden

Research Site, Cebu City, Philippines

Research Site, Dundee, United Kingdom

Research Site, Skrivarp, Sweden

Research Site, Plymouth, United Kingdom

Research Site, Nürberg, Germany

Research Site, Helsinki, Finland

Research Site, Essen, Germany

Research Site, Bexhill-on-Sea, United Kingdom

Research Site, Slough, United Kingdom

Research Site, West Midlands, United Kingdom

Research Site, Birmingham, United Kingdom

Research Site, Quezon City, Philippines

Research Site, Mannheim, Germany

Research Site, Brisbane, Australia

Research Site, Radstock, United Kingdom

Research Site, Dalby, Sweden

Research Site, Gubbio, Italy

Research Site, Aschaffenburg, Germany

Research Site, Firenze, Italy

Research Site, Joensuu, Finland

Research Site, Tampere, Finland

Research Site, Geelong, Australia

Research Site, Aberdeen, United Kingdom

Research Site, Oskarshamn, Sweden

Research Site, Perth, Australia

Research Site, Desio, Italy

Research Site, Mikkeli, Finland

Research Site, Udine, Italy

Research Site, Salo, Finland

Research Site, Arenzano, Italy

Research Site, Reggio Calabria, Italy

Research Site, Rho, Italy

Research Site, Bangalore, India

Research Site, Manchester, United Kingdom

Research Site, Bath, United Kingdom

Research Site, Roma, Italy

Research Site, Berlin, Germany

Research Site, Bolton, United Kingdom

Research Site, Coventry, United Kingdom

Research Site, Padova, Italy

Research Site, Skene, Sweden

Research Site, Heidelberg, Germany

Research Site, Kubang Kerian, Kota Bharu, Malaysia

Research Site, Winnipeg, Manitoba, Canada

Research Site, St. John's, Newfoundland and Labrador, Canada

Research Site, Etobicoke, Ontario, Canada

Research Site, Hamilton, Ontario, Canada

Research Site, Hastings, Ontario, Canada

Research Site, Kingston, Ontario, Canada

Research Site, North York, Ontario, Canada

Research Site, Ottawa, Ontario, Canada

Research Site, Smith Falls, Ontario, Canada

Research Site, Toronto, Ontario, Canada

Research Site, Chomedey-Laval, Quebec, Canada

Research Site, Laval, Quebec, Canada

Research Site, Montréal, Quebec, Canada

Starting date: July 2004
Last updated: July 27, 2006