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

NCT ID: NCT00770653

Last Updated: 2010-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 305 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2009-05-31

Brief Summary

The purpose of this study is to compare pioglitazone and metformin combination therapy, twice daily (BID), to glimepiride and metformin combination therapy for treating diabetic subjects with dyslipidemia.

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.

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

Conditions

Diabetes Mellitus; Dyslipidemias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pioglitazone 15 mg and Metformin 850 mg BID

Group Type: EXPERIMENTAL

Pioglitazone and Metformin

Intervention Type: DRUG

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.

Glimepiride 2 mg and Metformin 850 mg BID

Group Type: ACTIVE_COMPARATOR

Glimepiride and Metformin

Intervention Type: DRUG

Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Interventions

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.

Intervention Type: DRUG

Glimepiride and Metformin

Pioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

ACTOS®; AD-4833; OPIMET; Amaryl; Glista

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Takeda Pharma GmbH, Aachen (Germany)

Principal Investigators

Medical Adviser Clinical Research

Role: STUDY_DIRECTOR

Takeda Pharma Gmbh, Aachen (Germany)

Locations

Bretten, Baden-Wurttemberg, Germany

Deggingen, Baden-Wurttemberg, Germany

Dettenheim, Baden-Wurttemberg, Germany

Künzelsau, Baden-Wurttemberg, Germany

Rottweil, Baden-Wurttemberg, Germany

Spaichingen, Baden-Wurttemberg, Germany

Stockach, Baden-Wurttemberg, Germany

Wangen, Baden-Wurttemberg, Germany

Augsburg, Bavaria, Germany

Feldafing, Bavaria, Germany

Furth im Wald, Bavaria, Germany

Immenstadt im Allgäu, Bavaria, Germany

Lichtenfels, Bavaria, Germany

München, Bavaria, Germany

Schweinfurt, Bavaria, Germany

Waldkraiburg, Bavaria, Germany

Wallerfing, Bavaria, Germany

Weilersbach, Bavaria, Germany

Würzburg, Bavaria, Germany

Ketzin, Brandenburg, Germany

Rüdersdorf, Brandenburg, Germany

Bermerhaven, City state Bremen, Germany

Hamburg, City state of Hamburg, Germany

Bensheim, Hesse, Germany

Ehrenberg, Hesse, Germany

Gersfeld, Hesse, Germany

Kassel, Hesse, Germany

Kelkheim, Hesse, Germany

Offenbach, Hesse, Germany

Celle, Lower Saxony, Germany

Einbeck, Lower Saxony, Germany

Hanover, Lower Saxony, Germany

Hildesheim, Lower Saxony, Germany

Schwerin, Mecklenburg-Vorpommern, Germany

Bad Berleburg, North Rhine-Westphalia, Germany

Bad Laasphe, North Rhine-Westphalia, Germany

Bad Oeynhausen, North Rhine-Westphalia, Germany

Bocholt, North Rhine-Westphalia, Germany

Cologne, North Rhine-Westphalia, Germany

Dinslaken, North Rhine-Westphalia, Germany

Dorsten, North Rhine-Westphalia, Germany

Duisburg, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Frechen, North Rhine-Westphalia, Germany

Isselburg, North Rhine-Westphalia, Germany

Kamen, North Rhine-Westphalia, Germany

Marl, North Rhine-Westphalia, Germany

Menden, North Rhine-Westphalia, Germany

Münster, North Rhine-Westphalia, Germany

Siegen, North Rhine-Westphalia, Germany

Diez, Rhineland-Palatinate, Germany

Mainz, Rhineland-Palatinate, Germany

Neuwied, Rhineland-Palatinate, Germany

Rodenbach, Rhineland-Palatinate, Germany

Simmern, Rhineland-Palatinate, Germany

Borna, Saxony, Germany

Dresden, Saxony, Germany

Meissen, Saxony, Germany

Mittweida, Saxony, Germany

Magdeburg, Saxony-Anhalt, Germany

Reinfeld, Schleswig-Holstein, Germany

Berlin, State of Berlin, Germany

Altenburg, Thuringia, Germany

Blankenhain, Thuringia, Germany

Countries

Germany

References

Pfutzner A, Schondorf T, Tschope D, Lobmann R, Merke J, Muller J, Lehmann U, Fuchs W, Forst T. PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia. Diabetes Technol Ther. 2011 Jun;13(6):637-43. doi: 10.1089/dia.2010.0233. Epub 2011 Apr 2.

Reference Type: DERIVED

PMID: 21457065 (View on PubMed)

Related Links

http://general.takedapharm.com/content/file/pi.pdf?applicationcode=ab2d7112-8eb3-465a-8fda-35018a9eafb0&fileTypeCode=ACTOPLUSMETPI

ACTOPLUS MET® Package Insert

Other Identifiers

2006-004455-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-PIO-114

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1114-1678

Identifier Type: REGISTRY

Identifier Source: secondary_id

ATS K024

Identifier Type: -

Identifier Source: org_study_id