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

Primary Purpose

Diabetes Mellitus

Status

Completed

Phase

Phase 3

Locations

Germany

Study Type

Interventional

Intervention

Pioglitazone and Glimepiride

Glimepiride

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

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

Glimepiride 4 mg to 6 mg QD

Arm Description

Outcomes

Primary Outcome Measures

Change from Baseline in Homeostatic Model Assessment - Beta cell.

Secondary Outcome Measures

Change from Baseline in Glycosylated Hemoglobin.

Change from Baseline in oral glucose tolerance testing.

Change from Baseline in Insulin.

Change from Baseline in Proinsulin.

Change from Baseline in C-peptide.

Change from Baseline in High sensitivity C-Reactive Protein.

Change from Baseline in Adiponectin.

Change from Baseline in Homeostatic Model Assessment - Sensitivity.

Change from Baseline in Triglycerides

Change from Baseline in Low Density Lipoprotein-Cholesterol

Change from Baseline in High Density Lipoprotein-Cholesterol

Change from Baseline in Total Cholesterol

Full Information

NCT ID

NCT00770952

First Posted

October 9, 2008

Last Updated

July 1, 2010

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT00770952

Brief Title

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

Official Title

Effects of Pioglitazone in Combination With Glimepiride in Comparison to Glimepiride Monotherapy on Metabolic Control in Patients With Type 2 Diabetes Mellitus

Study Type

Interventional

2. Study Status

Record Verification Date

July 2010

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus

Keywords

Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

91 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Title

Glimepiride 4 mg to 6 mg QD

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Pioglitazone and Glimepiride

Other Intervention Name(s)

ACTOS®

Intervention Description

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

Intervention Name(s)

Glimepiride

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change from Baseline in Homeostatic Model Assessment - Beta cell.

Time Frame