Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.

NCT ID: NCT00770952

Last Updated: 2010-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2008-12-31

Brief Summary

The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and glimepiride combination therapy compared to glimepiride monotherapy in subjects with Type 2 Diabetes.

Detailed Description

Tight glycemic control is mandatory for the prevention and treatment of vascular complications in patients suffering from diabetes mellitus. After onset of Type 2 Diabetes, patients are usually treated with diet along with or without different combinations of oral drugs. One first-line drug class are sulfonylurea drugs that are preferably provided to patients who are not obese. The mode of action of sulfonylurea drugs is to increase beta-cell secretion, but it could be shown that they lead to deterioration of the beta-cell secretion product over time, resulting in increased proinsulin secretion. Since proinsulin is an independent cardiovascular risk factor, recent publications have demonstrated an increased risk for cardiovascular events in patients treated with sulfonylurea drugs as compared to other treatment methods.

Combination therapy of sulfonylurea drugs with glitazones has been shown to counterbalance the effect of deteriorated beta-cell secretion and to improve insulin sensitivity and the levels of proinsulin, C-peptide and other laboratory surrogate markers for cardiovascular risk. Proving that the treatment of diabetic patients with higher doses of beta cytotropic agents can be avoided and beta-cell function can be preserved by using pioglitazone in combination with low dose sulfonylurea drugs, it will be possible to optimize the treatment of patients with type 2 diabetes who are not controlled efficiently by sulfonylurea drugs monotherapy.

In this study patients will be enrolled who are inefficiently treated with a Glimepiride monotherapy. Patients will be either randomized to a combinational therapy of Pioglitazone and Glimepiride or Glimepiride monotherapy. If possible, study medication will be up-titrated to maximal dosage levels in both treatment arms to observe maximal and comparable treatment effects. Stable effects on beta-cell function will be observed after 24 weeks of treatment.

Conditions

Diabetes Mellitus

Study Design

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

Study Groups

Pioglitazone 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QD

Group Type: EXPERIMENTAL

Pioglitazone and Glimepiride

Intervention Type: DRUG

Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 2 mg, tablets, orally once daily for two weeks; increased to:

Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 4 mg, tablets, orally, once daily for two weeks; increased to:

Pioglitazone 45 mg, tablets, orally, once daily and Glimepiride 4 mg, orally, once daily for up to 20 weeks.

Glimepiride 4 mg to 6 mg QD

Group Type: ACTIVE_COMPARATOR

Glimepiride

Intervention Type: DRUG

Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 4 mg, tablets, orally once daily for two weeks; increased to:

Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 5 mg, tablets, orally once daily for two weeks; increased to:

Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 6 mg, tablets, orally once daily for up to 20 weeks.

Interventions

Pioglitazone and Glimepiride

Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 2 mg, tablets, orally once daily for two weeks; increased to:

Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 4 mg, tablets, orally, once daily for two weeks; increased to:

Pioglitazone 45 mg, tablets, orally, once daily and Glimepiride 4 mg, orally, once daily for up to 20 weeks.

Intervention Type: DRUG

Glimepiride

Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 4 mg, tablets, orally once daily for two weeks; increased to:

Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 5 mg, tablets, orally once daily for two weeks; increased to:

Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 6 mg, tablets, orally once daily for up to 20 weeks.

Intervention Type: DRUG

Other Intervention Names

ACTOS®

Eligibility Criteria

Inclusion Criteria

• Type 2 Diabetes according to the American Diabetes Association Criteria.
• Treatment with Glimepiride monotherapy (1-3 mg per day) 3 months before entering the study.
• Glycosylated hemoglobin greater than 6.5%, but less than 8.5% and/ or fasting plasma glucose greater than 7 mmol/l within the last 4 weeks.
• 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.
• History of hypersensitivity to the study drugs or to drugs with similar chemical structures.
• Progressive fatal disease.
• History of drug or alcohol abuse during the last 5 years.
• More than one unexplained episode of severe hypoglycemia within 6 months prior to entering the study.
• A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.8 mg/dl; glomerular filtration rate less than 40 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease, history of macular edema.
• Blood donation within the last 30 days.
• 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:

• CYP2C9 inductors
• CYP2C9 inhibitors
• rifampicin
• fluconazole
• drugs used for treating type 2 diabetes (insulin, insulin analogous compounds and oral antidiabetic drugs)
• Pretreatment with thiazolidinediones within the last 12 months.

• Minimum Eligible Age: 30 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

Villingen-Schwenningen, Baden-Wurttemberg, Germany

Aschaffenburg, Bavaria, Germany

Ingolstadt, Bavaria, Germany

Frankfurt am Main, Hesse, Germany

Frielendorf, Hesse, Germany

Rotenburg an der Fulda, Hesse, Germany

Hanover, Lower Saxony, Germany

Dortmund, North Rhine-Westphalia, Germany

Siegen, North Rhine-Westphalia, Germany

Kallstadt, Rhineland-Palatinate, Germany

Mainz, Rhineland-Palatinate, Germany

Mayen, Rhineland-Palatinate, Germany

Neuwied, Rhineland-Palatinate, Germany

Rhaunen, Rhineland-Palatinate, Germany

Friedrichsthal, Saarland, Germany

Meissen, Saxony, Germany

Berlin, State of Berlin, Germany

Countries

Germany

Related Links

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

ACTOS® Package Insert

Other Identifiers

2006-002271-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-PIO-112

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1114-3221

Identifier Type: REGISTRY

Identifier Source: secondary_id

ATS K020

Identifier Type: -

Identifier Source: org_study_id