Efficacy Study of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.

Condition(s) targeted: Diabetes Mellitus; Dyslipidemias

Intervention: Pioglitazone and metformin (Drug); Glimepiride and metformin (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Takeda Pharma GmbH

Official(s) and/or principal investigator(s):
Medical Adviser Clinical Research, Study Director, Affiliation: Takeda Pharma GmbH

Overall contact:
Study Manager, Phone: +49 800 8253325

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.

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

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

Primary outcome: The mean increase from Baseline in high-density lipoprotein cholesterol.

Secondary outcome:

Change from Baseline in Lipid profile (high-density lipoprotein cholesterol, high-density lipoprotein /low-density lipoprotein ratio and triglycerides).

Change from Baseline in Lipid profile (low-density lipoprotein subfractions, low-density lipoprotein cholesterol and total cholesterol).

Change from Baseline in Glycemic control (glycosylated hemoglobin, fasting insulin, fasting glucose, fasting intact proinsulin, adiponectin).

Change from Baseline in Inflammation (high sensitivity C-reactive protein).

Change from Baseline in blood pressure.

Change from Baseline in Inflammation: (Soluble CD40 Ligand, Matrix Metallo Proteinase-9, Soluble Intracellular Adhesion molecule and Soluble Vascular Cell Adhesion Molecule).

Change from Baseline in Thrombocyte function (Thromboxane B2, platelet function as assessed by PFA 100, Nitrotyrosine, E-Selectin, von-Willebrand Factor and erythrocyte deformability).

Compliance to treatment: intake of study medication greater than 80% and less than 120%.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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.

Study Manager, Phone: +49 800 8253325

Berlin, Germany; Recruiting

Hamburg, Germany; Recruiting

Spaichingen, Baden-Württemberg, Germany; Recruiting

Rottweil, Baden-Württemberg, Germany; Recruiting

Künzelsau, Baden-Württemberg, Germany; Recruiting

Deggingen, Baden-Württemberg, Germany; Recruiting

Stockach, Baden-Württemberg, Germany; Recruiting

Bretten, Baden-Württemberg, Germany; Recruiting

Wangen, Baden-Württemberg, Germany; Recruiting

Dettenheim, Baden-Württemberg, Germany; Recruiting

Augsburg, Bayern, Germany; Recruiting

Immenstadt, Bayern, Germany; Recruiting

Furth im Wald, Bayern, Germany; Recruiting

Wallerfing, Bayern, Germany; Recruiting

Weilersbach, Bayern, Germany; Recruiting

Feldafing, Bayern, Germany; Recruiting

Schweinfurt, Bayern, Germany; Recruiting

München, Bayern, Germany; Recruiting

Würzburg, Bayern, Germany; Recruiting

Waldkraiburg, Bayern, Germany; Recruiting

Lichtenfels, Bayern, Germany; Recruiting

Rüdersdorf, Brandenburg, Germany; Recruiting

Ketzin, Brandenburg, Germany; Recruiting

Bermerhaven, Bremen, Germany; Recruiting

Gersfeld, Hessen, Germany; Recruiting

Ehrenberg, Hessen, Germany; Recruiting

Bensheim, Hessen, Germany; Recruiting

Kassel, Hessen, Germany; Recruiting

Kelkheim, Hessen, Germany; Recruiting

Offenbach, Hessen, Germany; Recruiting

Schwerin, Mecklenburg-Vorpommern, Germany; Recruiting

Hildesheim, Niedersachsen, Germany; Recruiting

Einbeck, Niedersachsen, Germany; Recruiting

Hannover, Niedersachsen, Germany; Recruiting

Celle, Niedersachsen, Germany; Recruiting

Bocholt, Nordrhein-Westfalen, Germany; Recruiting

Isselburg, Nordrhein-Westfalen, Germany; Recruiting

Dorsten, Nordrhein-Westfalen, Germany; Recruiting

Bad Berleburg, Nordrhein-Westfalen, Germany; Recruiting

Menden, Nordrhein-Westfalen, Germany; Recruiting

Essen, Nordrhein-Westfalen, Germany; Recruiting

Duisburg, Nordrhein-Westfalen, Germany; Recruiting

Kamen, Nordrhein-Westfalen, Germany; Recruiting

Marl, Nordrhein-Westfalen, Germany; Recruiting

Münster, Nordrhein-Westfalen, Germany; Recruiting

Dinslaken, Nordrhein-Westfalen, Germany; Recruiting

Bad Oeynhausen, Nordrhein-Westfalen, Germany; Recruiting

Köln, Nordrhein-Westfalen, Germany; Recruiting

Siegen, Nordrhein-Westfalen, Germany; Recruiting

Frechen, Nordrhein-Westfalen, Germany; Recruiting

Bad Laasphe, Nordrhein-Westfalen, Germany; Recruiting

Neuwied, Rheinland-Pfalz, Germany; Recruiting

Diez, Rheinland-Pfalz, Germany; Recruiting

Mainz, Rheinland-Pfalz, Germany; Recruiting

Simmern, Rheinland-Pfalz, Germany; Recruiting

Rodenbach, Rheinland-Pfalz, Germany; Recruiting

Dresden, Sachsen, Germany; Recruiting

Meißen, Sachsen, Germany; Recruiting

Mittweida, Sachsen, Germany; Recruiting

Borna, Sachsen, Germany; Recruiting

Magdeburg, Sachsen-Anhalt, Germany; Recruiting

Reinfeld, Schleswig-Holstein, Germany; Recruiting

Blankenhain, Thüringen, Germany; Recruiting

Altenburg, Thüringen, Germany; Recruiting

ACTOS® Package Insert

FDA Safety Alerts and Recalls

Starting date: April 2007
Ending date: March 2009
Last updated: October 9, 2008