ARAMIS: Actions of tesaglitazaR on fAt Metabolism and Insulin Sensitivity

Study Overview
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Brief Summary
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This is a 16-week randomized, double-blind, parallel-group, multi-center, placebo- and active- (metformin 1.5 g) controlled study of tesaglitazar (1 mg) in patients with type 2 diabetes. After a 1-week enrollment period, a 3 week placebo single blind run in period and 1-week placebo single-blind baseline measurement period, the patients will be given the investigational product for 16 weeks in a double blind fashion. Metformin will be titrated up during the first 3 weeks of the double-blind period. The total study duration, including enrollment, run-in, randomized treatment and follow-up, is 29 weeks.

Official Title
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A 16-Week Randomized, Double-Blind, Parallel-Group, Multicenter, Placebo- and Active- (Metformin) Controlled Study to Evaluate the Effect on Whole Body Insulin Sensitivity of Tesaglitazar Therapy When Administered to Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Tesaglitazar
* Drug: Metformin
* Behavioral: Dietary and lifestyle modification counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of a written informed consent Men or women who are 30-70 years of age Female patients: postmenopausal, hysterectomized 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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tesaglitazar|nan|
|Drug: Metformin|nan|
|Behavioral: Dietary and lifestyle modification counseling|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole-body insulin sensitivity by assessing the M value during high (80 mU/m2/min) insulin level euglycemic hyperinsulinemic clamp. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic and peripheral insulin sensitivity by assessing the M value during low (20 mU/m2/min) insulin level euglycemic hyperinsulinemic clamp. |  |  | 
| Basal hepatic glucose output measured by dideuterated glucose in the fasting state and during low insulin level clamp. |  |  | 
| Plasma profile of glucose, insulin and lipids after a mixed meal |  |  | 
| Calculated insulin secretion |  |  | 
| Liver oxidation after a mixed meal |  |  | 
| 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 |  |  | 
| Waist and hip circumference |  |  | 
| Laboratory efficacy variables (lipids, inflammatory marker and adipose tissue hormones) |  |  | 
| Safety and tolerability of tesaglitazar in patients with type 2 diabetes. |  |  |