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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00770952
First received: October 9, 2008
Last updated: July 1, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Drug: Pioglitazone and Glimepiride
Drug: Glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Pioglitazone in Combination With Glimepiride in Comparison to Glimepiride Monotherapy on Metabolic Control in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from Baseline in Homeostatic Model Assessment - Beta cell. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in oral glucose tolerance testing. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Insulin. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Proinsulin. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in C-peptide. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in High sensitivity C-Reactive Protein. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Adiponectin. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Homeostatic Model Assessment - Sensitivity. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Triglycerides [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Low Density Lipoprotein-Cholesterol [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in High Density Lipoprotein-Cholesterol [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in Total Cholesterol [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]

Enrollment: 91
Study Start Date: December 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QD Drug: 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.

Other Name: ACTOS®
Active Comparator: Glimepiride 4 mg to 6 mg QD 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.


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.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770952

Locations
Germany
Villingen-Schwenningen, Baden-Württemberg, Germany
Aschaffenburg, Bayern, Germany
Ingolstadt, Bayern, Germany
Frankfurt, Hessen, Germany
Frielendorf, Hessen, Germany
Rotenburg, Hessen, Germany
Hannover, Niedersachsen, Germany
Dortmund, Nordrhein-Westfalen, Germany
Siegen, Nordrhein-Westfalen, Germany
Kallstadt, Rheinland-Pfalz, Germany
Mainz, Rheinland-Pfalz, Germany
Mayen, Rheinland-Pfalz, Germany
Neuwied, Rheinland-Pfalz, Germany
Rhaunen, Rheinland-Pfalz, Germany
Friedrichsthal, Saarland, Germany
Meißen, Sachsen, Germany
Berlin, Germany
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Adviser Clinical Research Takeda Pharma Gmbh, Aachen (Germany)
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Director, Takeda Pharma GmbH, Aachen (Germany)
ClinicalTrials.gov Identifier: NCT00770952     History of Changes
Other Study ID Numbers: ATS K020, 2006-002271-41, D-PIO-112, U1111-1114-3221
Study First Received: October 9, 2008
Last Updated: July 1, 2010
Health Authority: European Union: European Medicines Agency

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Glimepiride
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 16, 2014