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
Sponsored by
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
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
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
No
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
Week: 24 or Final Visit beyond week 12.
Secondary Outcome Measure Information:
Title
Change from Baseline in Glycosylated Hemoglobin.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in oral glucose tolerance testing.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Insulin.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Proinsulin.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in C-peptide.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in High sensitivity C-Reactive Protein.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Adiponectin.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Homeostatic Model Assessment - Sensitivity.
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Triglycerides
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Low Density Lipoprotein-Cholesterol
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in High Density Lipoprotein-Cholesterol
Time Frame
Week: 24 or Final Visit beyond week 12.
Title
Change from Baseline in Total Cholesterol
Time Frame
Week: 24 or Final Visit beyond week 12.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Adviser Clinical Research
Organizational Affiliation
Takeda Pharma Gmbh, Aachen (Germany)
Official's Role
Study Director
Facility Information:
City
Villingen-Schwenningen
State/Province
Baden-Württemberg
Country
Germany
City
Aschaffenburg
State/Province
Bayern
Country
Germany
City
Ingolstadt
State/Province
Bayern
Country
Germany
City
Frankfurt
State/Province
Hessen
Country
Germany
City
Frielendorf
State/Province
Hessen
Country
Germany
City
Rotenburg
State/Province
Hessen
Country
Germany
City
Hannover
State/Province
Niedersachsen
Country
Germany
City
Dortmund
State/Province
Nordrhein-Westfalen
Country
Germany
City
Siegen
State/Province
Nordrhein-Westfalen
Country
Germany
City
Kallstadt
State/Province
Rheinland-Pfalz
Country
Germany
City
Mainz
State/Province
Rheinland-Pfalz
Country
Germany
City
Mayen
State/Province
Rheinland-Pfalz
Country
Germany
City
Neuwied
State/Province
Rheinland-Pfalz
Country
Germany
City
Rhaunen
State/Province
Rheinland-Pfalz
Country
Germany
City
Friedrichsthal
State/Province
Saarland
Country
Germany
City
Meißen
State/Province
Sachsen
Country
Germany
City
Berlin
Country
Germany
12. IPD Sharing Statement
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Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.
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