Official Title: “Effects of a Pioglitazone/Metformin Fixed Combination in Comparison to Metformin in Combination With Glimepiride on Diabetic Dyslipidemia”

The purpose of this study is to compare pioglitazone and metformin combination therapy to glimepiride and metformin combination therapy for treating diabetic subjects with dyslipidemia.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2009

Insulin resistance is a major endocrinopathy preceding the development of hyperglycemia, diabetic dyslipidemia and cardiovascular disease in type 2 diabetes. The most common pattern of dyslipidemia in patients with type 2 diabetes are elevated triglyceride levels, decreased hih-density lipoprotein cholesterol and a predominance of small dense low-density lipoprotein particles. Each of these dyslipidemia features is associated with an increased risk of cardiovascular events.

Pioglitazone and Metformin are established drugs which can be used for the treatment of type 2 diabetes. This study will investigate the effects of treatment with fixed Pioglitazone/Metformin combination therapy of Metformin and Glimepiride in Metformin-pretreated type 2 diabetic patients with dyslipidemia.

Total participation time in this study is anticipated to be approximately 24 weeks.

Intervention(s) in this Clinical Trial

• Drug: Pioglitazone and metformin
  • Pioglitazone 15 mg/metformin 850 mg combination tablets, orally, twice daily and glimepiride placebo-matching tablets, orally, once daily and metformin placebo-matching tablets, orally, twice daily for up to 24 weeks.
• Drug: Glimepiride and metformin
  • Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 1 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Active Comparator: 2

Primary Measures

• The mean increase from Baseline in High-Density Lipoprotein Cholesterol.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No

Secondary Measures

• Change from Baseline in High-Density Lipoprotein Cholesterol.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Triglycerides.
  • Time Frame: Weeks 8, 16, and 24 or Final Visit.
    Safety Issue?: No
• Change from Baseline in Low-Density Lipoprotein Subfractions.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Low-Density Lipoprotein Cholesterol.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Glycosylated Hemoglobin.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Fasting Glucose.
  • Time Frame: Weeks 8, 16, and 24 or Final Visit.
    Safety Issue?: No
• Change from Baseline in Fasting Intact Proinsulin.
  • Time Frame: Weeks 8, 16, and 24 or Final Visit.
    Safety Issue?: No
• Change from Baseline in Adiponectin.
  • Time Frame: Weeks 8, 16, and 24 or Final Visit.
    Safety Issue?: No
• Change from Baseline in High Sensitivity C-reactive Protein.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Blood Pressure
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Soluble CD40 Ligand.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Matrix Metallo Proteinase-9.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Soluble Intracellular Adhesion molecule.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Soluble Vascular Cell Adhesion Molecule.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Thromboxane B2.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Platelet Function.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Nitrotyrosine.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in E-Selectin.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Von-Willebrand Factor.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Change from Baseline in Erythrocyte Deformability.
  • Time Frame: Week 24 or Final Visit
    Safety Issue?: No
• Intake of study medication greater than 80%.
  • Time Frame: Weeks 8, 16, and 24 or Final Visit.
    Safety Issue?: No
• Intake of study medication less than 120%
  • Time Frame: Weeks 8, 16, and 24 or Final Visit.
    Safety Issue?: No

Inclusion Criteria:

• Type 2 diabetes according to the American Diabetes Association Criteria.
• Treatment with individual maximal tolerated dose of metformin (850 - 2000 mg) as monotherapy within the last 12 weeks.
• Glycosylated Hemoglobin greater than or equal to 6.5% and less than or equal to 9%.
• Dyslipidemia defined as high-density lipoprotein cholesterol less than or equal to 1.03 mmol/l (40 mg/dL) and/or triglycerides greater than or equal to 1.7 mmol/l (150 mg/dL).
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria:

• Type 1 diabetes mellitus.
• Insulin-dependent type 2 diabetes mellitus.
• Treatment or history of treatment with any insulin formulation other than emergency for more than 2 weeks.
• Treatment with other oral antidiabetic drugs in addition to metformin within the last 12 weeks.
• Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
• Heparin (and heparin-like drugs)
• coumarin
• phenprocoumon
• hirudin
• Protein C
• Fondaparinux
• antithrombin III
• Peroxisome Proliferation Activating Receptor (gamma) agonists
• Treatment within the last 12 weeks with:
• fibrates
• gemfibrozil
• niacin
• months
• Rifampicin
• Changes in dosage of any statin treatment to lower low-density lipoprotein within 2 weeks before study entry and during study participation interval.
• Changes in dosage of any anticoagulant treatment with acetyl salicylic acid and/or clopidogrel within 2 weeks before study entry and during study participation interval.
• Start of statin and/or anticoagulant treatment during study participation interval.
• History of severe or multiple allergies and/ or acute severe infections.
• Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit.
• Progressive fatal disease.
• Any elective surgery during study participation.
• History of drug or alcohol abuse within the last 5 years.
• A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase and/or aspartate aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.2 mg/dL in women and greater than 1.5 mg/dL in men, glomerular filtration rate less than 60 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease as judged by the investigator, history of macular edema.
• Blood donation within the last 30 days.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Pharma GmbH

Overall Clinical Trial Officials and Contacts

Medical Adviser Clinical Research Study Director Takeda Pharma GmbH  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00770653

Study ID Number: ATS K024

ClinicalTrials.gov Identifier: NCT00770653

Health Authority: European Union: European Medicines Agency

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