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24-Hour Glycemia: Rosiglitazone Versus Glimepiride In Type 2 Diabetes

Primary Purpose

Non-Insulin-Dependent Diabetes Mellitus

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
rosiglitazone-metformin fixed dose combination
metformin + glimepiride
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Insulin-Dependent Diabetes Mellitus focused on measuring type 2 diabetes, rosiglitazone, metformin, glimepiride, glycemia

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Males and females aged 40 to 80 years Diagnosis of type 2 diabetes mellitus for at least 6 months Body mass index (BMI) ≥25kg/m2 7%≥HbA1c ≤ 9% at visit 2 Treatment with metformin between 1.7g/day and 3g/day for at least 12 weeks prior to visit 1 Female subjects must be non-pregnant, post-menopausal, surgically sterile or using effective contraceptive measures Written informed consent Exclusion Criteria: Use of any oral antidiabetic drug other than metformin within 12 weeks prior to screening Significant hypersensitivity to thiazolidinediones and sulfonylureas or compounds with similar chemical structure Subjects who have required the use of insulin for glycaemic control at any time in the past or subject with a history of metabolic acidosis including diabetic ketoacidosis Subjects with clinically significant ongoing oedema or with a history of oedema in the 12 months prior to visit 1 Subjects with a history of severe hypoglycaemia Anemia defined by haemoglobin concentration <11.0g/dL for males or <10.0g/dL for females Renal disease or renal dysfunction, e.g. as suggested by serum creatinine levels ≥135µmol/L in males and ≥110µmol/L in females Presence of clinically significant hepatic disease (i.e. ALT, AST, total bilirubin or alkaline phosphatase >2.5 times the upper limit of the normal reference range) Congestive heart failure (NYHA class I to IV), unstable or severe angina, recent myocardial infarction Subjects with chronic diseases requiring periodic or intermittent treatment with oral or intravenous corticosteroids Female who are lactating, pregnant, or planning to become pregnant Any clinically significant abnormality identified at screening which in the judgement of the investigator makes the subject unsuitable for inclusion in the study (e.g. physical examination, laboratory test, ECG, ...) Use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to enrolment in this study Active alcohol, drug or medication abuse within the last 6 months or any condition that would indicate the likelihood of poor subject compliance Subjects not willing to comply with the procedures described in this protocol.

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Duration of Hyperglycaemia (>126 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Episodes of Hyperglycaemia (>126 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.

    Secondary Outcome Measures

    Duration of Severe Hyperglycaemia (>150 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Episodes of Severe Hyperglycaemia (>150 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Duration of Hypoglycaemia (<80 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Episodes of Hypoglycaemia (<80 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Duration of Hypoglycaemia (<60 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Episodes of Hypoglycaemia (<60 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    HbA1c (Glycosylated Hemoglobin)
    Uncontrolled HbA1c>8.5%. HbA1c and fasting blood glucose taken at hospital
    8-Iso Prostaglandin F2α (8-iso PGF2α) Excretion Rate
    8-Iso Prostaglandin F2α (8-iso PGF2α) excretion rate measured during the 24 hours preceding the CGM system removal. The nocturnal glycemia measured by CGM system will be defined as the average of glycemic values collected between midnight and breakfast time.
    Glycaemia According to CGMS (Nocturnal), mg/dL
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The nocturnal glycemia measured by CGM system will be defined as the average of glycemic values collected between midnight and breakfast time.
    Glycaemia According to CGMS (Diurnal), mg/dL
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The diurnal glycemia measured by CGM system will be the average of glycemic values recorded between breakfast time and midnight.
    Glycaemia According to CGMS (Dawn), mg/dL
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The glycemia "at dawn" measured by CGM system will be defined as the average of glycemic values recorded between 4 AM and breakfast time.
    Glycaemia According to CGMS (Total Area Under the Curve (AUC) for Values Above 1 mg/dL), mg/dL
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system.
    Glycaemia According to CGMS (Postprandial Incremental AUC or Values Above 1 mg/dL), mg/dL
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system.
    Glycaemia According to CGMS (Basal Incremental AUC or Values Above 1 mg/dL), mg/dL
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system.
    Glycaemia According to CGMS (MAGE), mg/dL
    Calculation of the Mean amplitude of glycemic excursion (MAGE) was obtained by measuring the arithmetic mean of the major glucose concentration increases or decreases on days 2 and 3 of glycaemic profile and then averaging results on the two days.

    Full Information

    First Posted
    April 25, 2006
    Last Updated
    April 10, 2009
    Sponsor
    GlaxoSmithKline
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00318656
    Brief Title
    24-Hour Glycemia: Rosiglitazone Versus Glimepiride In Type 2 Diabetes
    Official Title
    Comparison of the Effects of Rosiglitazone and Glimepiride, Both Given in Combination With Metformin, on 24-Hour Glycemia in Type 2 Diabetes Patients Not Controlled With Metformin Alone. A 3-Month Multicentre, Randomized, Parallel-Group, Open-Label Study.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2009
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2005 (undefined)
    Primary Completion Date
    October 2007 (Actual)
    Study Completion Date
    October 2007 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    GlaxoSmithKline

    4. Oversight

    5. Study Description

    Brief Summary
    A better glycemic control is associated with less complications (cardiac diseases, blindness, etcetera) for type 2 diabetic patients. The objective is to study if rosiglitazone may lead to a more regular glycemic pattern with less hyperglycemia and hypoglycemia episodes than with a sulphonylurea (glimepiride).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non-Insulin-Dependent Diabetes Mellitus
    Keywords
    type 2 diabetes, rosiglitazone, metformin, glimepiride, glycemia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    23 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    rosiglitazone-metformin fixed dose combination
    Intervention Type
    Drug
    Intervention Name(s)
    metformin + glimepiride
    Other Intervention Name(s)
    rosiglitazone-metformin fixed dose combination
    Primary Outcome Measure Information:
    Title
    Duration of Hyperglycaemia (>126 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    Episodes of Hyperglycaemia (>126 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Secondary Outcome Measure Information:
    Title
    Duration of Severe Hyperglycaemia (>150 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    Episodes of Severe Hyperglycaemia (>150 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    Duration of Hypoglycaemia (<80 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    Episodes of Hypoglycaemia (<80 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    Duration of Hypoglycaemia (<60 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    Episodes of Hypoglycaemia (<60 mg/dL) at Baseline Compared to After 12 Weeks on Treatment
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
    Time Frame
    Baseline and 12 weeks
    Title
    HbA1c (Glycosylated Hemoglobin)
    Description
    Uncontrolled HbA1c>8.5%. HbA1c and fasting blood glucose taken at hospital
    Time Frame
    Baseline and 12 weeks
    Title
    8-Iso Prostaglandin F2α (8-iso PGF2α) Excretion Rate
    Description
    8-Iso Prostaglandin F2α (8-iso PGF2α) excretion rate measured during the 24 hours preceding the CGM system removal. The nocturnal glycemia measured by CGM system will be defined as the average of glycemic values collected between midnight and breakfast time.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (Nocturnal), mg/dL
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The nocturnal glycemia measured by CGM system will be defined as the average of glycemic values collected between midnight and breakfast time.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (Diurnal), mg/dL
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The diurnal glycemia measured by CGM system will be the average of glycemic values recorded between breakfast time and midnight.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (Dawn), mg/dL
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The glycemia "at dawn" measured by CGM system will be defined as the average of glycemic values recorded between 4 AM and breakfast time.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (Total Area Under the Curve (AUC) for Values Above 1 mg/dL), mg/dL
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (Postprandial Incremental AUC or Values Above 1 mg/dL), mg/dL
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (Basal Incremental AUC or Values Above 1 mg/dL), mg/dL
    Description
    Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system.
    Time Frame
    Baseline and 12 weeks
    Title
    Glycaemia According to CGMS (MAGE), mg/dL
    Description
    Calculation of the Mean amplitude of glycemic excursion (MAGE) was obtained by measuring the arithmetic mean of the major glucose concentration increases or decreases on days 2 and 3 of glycaemic profile and then averaging results on the two days.
    Time Frame
    Baseline and 12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Males and females aged 40 to 80 years Diagnosis of type 2 diabetes mellitus for at least 6 months Body mass index (BMI) ≥25kg/m2 7%≥HbA1c ≤ 9% at visit 2 Treatment with metformin between 1.7g/day and 3g/day for at least 12 weeks prior to visit 1 Female subjects must be non-pregnant, post-menopausal, surgically sterile or using effective contraceptive measures Written informed consent Exclusion Criteria: Use of any oral antidiabetic drug other than metformin within 12 weeks prior to screening Significant hypersensitivity to thiazolidinediones and sulfonylureas or compounds with similar chemical structure Subjects who have required the use of insulin for glycaemic control at any time in the past or subject with a history of metabolic acidosis including diabetic ketoacidosis Subjects with clinically significant ongoing oedema or with a history of oedema in the 12 months prior to visit 1 Subjects with a history of severe hypoglycaemia Anemia defined by haemoglobin concentration <11.0g/dL for males or <10.0g/dL for females Renal disease or renal dysfunction, e.g. as suggested by serum creatinine levels ≥135µmol/L in males and ≥110µmol/L in females Presence of clinically significant hepatic disease (i.e. ALT, AST, total bilirubin or alkaline phosphatase >2.5 times the upper limit of the normal reference range) Congestive heart failure (NYHA class I to IV), unstable or severe angina, recent myocardial infarction Subjects with chronic diseases requiring periodic or intermittent treatment with oral or intravenous corticosteroids Female who are lactating, pregnant, or planning to become pregnant Any clinically significant abnormality identified at screening which in the judgement of the investigator makes the subject unsuitable for inclusion in the study (e.g. physical examination, laboratory test, ECG, ...) Use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to enrolment in this study Active alcohol, drug or medication abuse within the last 6 months or any condition that would indicate the likelihood of poor subject compliance Subjects not willing to comply with the procedures described in this protocol.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    GSK Clinical Trials, MD
    Organizational Affiliation
    GlaxoSmithKline
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22775317
    Citation
    Monnier L, Colette C, Comenducci A, Vallee D, Dejager S. Add-on therapies to metformin in type 2 diabetes: what modulates the respective decrements in postprandial and basal glucose? Diabetes Technol Ther. 2012 Oct;14(10):943-50. doi: 10.1089/dia.2012.0045. Epub 2012 Jul 9.
    Results Reference
    derived

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    24-Hour Glycemia: Rosiglitazone Versus Glimepiride In Type 2 Diabetes

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