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

October 9, 2008
July 1, 2010
December 2006
December 2008   (final data collection date for primary outcome measure)
Change from Baseline in Homeostatic Model Assessment - Beta cell. [ Time Frame: Week: 24 or Final Visit beyond week 12. ] [ Designated as safety issue: No ]
Change from Baseline in Homeostatic Model Assessment - Beta cell. [ Time Frame: Week: 24. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00770952 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in oral glucose tolerance testing (fasting glucose, glucose area under the Curve). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in Insulin (fasting, during oral glucose tolerance testing). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in Proinsulin (fasting, during oral glucose tolerance testing). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in C-peptide (fasting, during oral glucose tolerance testing). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in Lipids (triglycerides, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, total cholesterol). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in High sensitivity C-Reactive Protein (fasting, during oral glucose tolerance testing). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in Adiponectin (fasting, during oral glucose tolerance testing). [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
  • Change from Baseline in Homeostatic Model Assessment - Sensitivity. [ Time Frame: Week 24. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.
Effects of Pioglitazone in Combination With Glimepiride in Comparison to Glimepiride Monotherapy on Metabolic Control in Patients With Type 2 Diabetes Mellitus

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus
  • 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®
  • 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.

  • Experimental: Pioglitazone 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QD
    Intervention: Drug: Pioglitazone and Glimepiride
  • Active Comparator: Glimepiride 4 mg to 6 mg QD
    Intervention: Drug: Glimepiride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
91
December 2008
December 2008   (final data collection date for primary outcome measure)

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.
Both
30 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00770952
ATS K020, 2006-002271-41, D-PIO-112, U1111-1114-3221
No
Medical Director, Takeda Pharma GmbH, Aachen (Germany)
Takeda
Not Provided
Study Director: Medical Adviser Clinical Research Takeda Pharma Gmbh, Aachen (Germany)
Takeda
July 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP