Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
Primary Purpose
Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pioglitazone
Glyburide
Pioglitazone
Glyburide
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
- 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.
- Diagnosed with type 2 diabetes mellitus.
- Naive to oral antidiabetic pharmacologic therapy, who were currently taking sulfonylurea monotherapy, who were currently taking sulfonylurea/metformin combination therapy, or who were currently taking metformin monotherapy.
- Mild cardiac disease New York Heart Association functional Class I.
- Participated in dietary counseling.
- Glycosylated hemoglobin greater than or equal to 7.5% and less than 12% at Screening if naïve to oral antidiabetic pharmacologic therapy or taking metformin monotherapy, or greater than or equal to 6.5% and less than 12% if currently taking sulfonylurea monotherapy or taking ulfonylurea/metformin combination therapy.
- Stable therapy for cardiovascular dysfunction, defined as no change in therapy for greater than or equal to 4 weeks prior to Randomization.
Exclusion Criteria:
- Within the past 30 days treated with rosiglitazone, pioglitazone, or troglitazone or those previously treated with rosiglitazone, pioglitazone, or troglitazone but discontinued from therapy because of lack of efficacy or clinical or laboratory signs of intolerance.
- Treated with a sulfonylurea but discontinued for lack of efficacy or clinical or laboratory intolerance.
- Currently taking insulin or on continuous insulin therapy for control of their diabetes
- Type 1 (insulin-dependent) diabetes mellitus or a history of ketoacidosis.
- Any other investigational drug during the 30 days prior to Visit 1 or who will receive such a drug during the time-frame of this study.
- History of chronic alcoholism or drug abuse during the 6 months prior to the study.
- New York Heart Association functional Class II, III, or IV cardiac disease at Screening, or previous history of Class III or IV.
Any of the following:
- myocardial infarction
- coronary angioplasty or bypass graft
- unstable angina pectoris
- transient ischemic attacks
- documented cerebrovascular accident. 9. Abdominal, thoracic, or vascular surgery during the 3 months prior to Visit 1.
- Planned surgical or catheterization intervention within 6 months following Visit 1.
- Awaiting cardiac transplantation.
- Intercurrent illness severe enough to require hospitalization during the 3 weeks prior to Visit 1.
- Body mass index greater than 48 kg/m2 as calculated by [weight (kg)/height (m)2].
- Anemia having hemoglobin less than 10.5 g per dL for men and 10.0 g per dL for women.
- Triglyceride level greater than 500 mg per dL.
- Clinical evidence of active liver disease or alanine transaminase levels greater than 2.5 times the upper limit of normal.
- Serum creatinine greater than 2.0 mg per dL for men and 1.8 mg per dL for women or urinalysis protein (albumin) excretion levels greater than 2 plus on Combistix or equivalent and on repeat 24-hour results with greater than 3 g macroproteinuria.
- Unstable coronary syndromes.
- Systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg at Screening.
- Serious uncontrolled cardiac rhythm disturbances.
- Symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm Hg.
- Severe, advanced peripheral vascular disease (limb-threatening ischemia) or claudication resulting in the inability to walk greater than 1 block or to climb 10 stairs without interruption.
- Lower extremity amputation that would prevent the patient from performing the exercise test.
- Any other serious disease or condition which might affect life-expectancy or make it difficult to successfully manage and follow the subjects according to the protocol.
- Unexplained clinically significant findings on chest x-ray.
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:
- Oral, injected, or inhaled corticosteroids of greater than 2 week duration, or the need for recurrent us of corticosteroids.
- Prescription niacin
- Anti-diabetic medications except metformin
- Cardiovascular medications must remain stable for at least 4 weeks prior to Randomization
- Non-steroidal anti-inflammatory drugs
- Aspirin greater than 325 mg per day
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Experimental
Active Comparator
Arm Label
Pioglitazone 15 mg to 45 mg QD
Glyburide 2.5 mg to 15 mg, QD
Pioglitazone 15 mg or 30 mg QD
Glyburide 5 mg or 10 mg, QD
Arm Description
Outcomes
Primary Outcome Measures
Change in the walking distance during a standardized 6-minute walk test.
Secondary Outcome Measures
Morbidity and Mortality Due to Cardiovascular Events.
Change in Cardiovascular Treatment Program.
Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate)
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass)
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction)
Change from Baseline in Electrocardiogram Parameter (Cardiac Index)
Change from Baseline in Electrocardiogram Parameter (Fractional Shortening)
Change in Blood Pressure
Change in Heart Rate
Change in Body Weight
Full Information
NCT ID
NCT00521742
First Posted
August 25, 2007
Last Updated
February 27, 2012
Sponsor
Takeda
Collaborators
Takeda Pharmaceuticals North America, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00521742
Brief Title
Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
Official Title
A Randomized, Double-Blind, Comparator-Controlled Study of Pioglitazone HCl vs Glyburide in the Treatment of Patients With Type 2 (Non-Insulin-Dependent) Diabetes Mellitus and Mild Cardiac Disease (NYHA I)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
March 2001 (undefined)
Primary Completion Date
January 2003 (Actual)
Study Completion Date
January 2003 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Takeda Pharmaceuticals North America, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the cardiovascular effects of pioglitazone, once daily (QD), versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease.
Detailed Description
Diabetes is a chronic disease involving multiple metabolic defects that include inadequate insulin activity and resultant hyperglycemia. Individuals' differing genetic predisposition, level of physical activity, and age all contribute to variations in the onset and severity of type 2 diabetes. However, progression of this disease typically follows a characteristic pattern that begins as a reduced sensitivity of hepatic and peripheral-tissues to circulating insulin (ie, insulin resistance). The body's decreasing ability to produce adequate insulin to overcome insulin resistance (ie, insulin deficiency due to beta-cell insufficiency) results in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 17 million people have diabetes, with type 2 diabetes occurring in approximately 90% to 95% of cases.
The goal of treating type 2 diabetes is to control blood glucose and thereby prevent long-term complications. Adequate glycemic control is paramount in attempting to avert chronic complications, including blindness, renal dysfunction and resultant dialysis or renal transplantation, neuropathy, and nontraumatic amputations. Intensive glucose management in the early stages of diabetes may help forestall complications.
Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. Glyburide, is an oral antidiabetic agent of the sulfonylurea class. The primary purpose of this study is to evaluate the cardiovascular effects of pioglitazone versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease
Study participation is anticipated to be approximately 1 year and 2 weeks.
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
300 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone 15 mg to 45 mg QD
Arm Type
Experimental
Arm Title
Glyburide 2.5 mg to 15 mg, QD
Arm Type
Active Comparator
Arm Title
Pioglitazone 15 mg or 30 mg QD
Arm Type
Experimental
Arm Title
Glyburide 5 mg or 10 mg, QD
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos, AD4833
Intervention Description
Pioglitazone 15 mg to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Glyburide
Intervention Description
Glyburide 2.5 mg to 15 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos, AD4833
Intervention Description
Pioglitazone 15 mg or 30 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally once daily for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Glyburide
Intervention Description
Glyburide 5 mg or 10 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally once daily for up to 52 weeks.
Primary Outcome Measure Information:
Title
Change in the walking distance during a standardized 6-minute walk test.
Time Frame
Weeks 2, 16, 24, 40, and 52 or Final Visit
Secondary Outcome Measure Information:
Title
Morbidity and Mortality Due to Cardiovascular Events.
Time Frame
At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit
Title
Change in Cardiovascular Treatment Program.
Time Frame
At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit
Title
Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate)
Time Frame
Weeks 24 and 52 or Final Visit
Title
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass)
Time Frame
Week 52 or Final Visit
Title
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction)
Time Frame
Week 52 or Final Visit
Title
Change from Baseline in Electrocardiogram Parameter (Cardiac Index)
Time Frame
Week 52 or Final Visit
Title
Change from Baseline in Electrocardiogram Parameter (Fractional Shortening)
Time Frame
Week 52 or Final Visit
Title
Change in Blood Pressure
Time Frame
Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
Title
Change in Heart Rate
Time Frame
Weeks 24 and 52 or Final Visit
Title
Change in Body Weight
Time Frame
Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
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.
Diagnosed with type 2 diabetes mellitus.
Naive to oral antidiabetic pharmacologic therapy, who were currently taking sulfonylurea monotherapy, who were currently taking sulfonylurea/metformin combination therapy, or who were currently taking metformin monotherapy.
Mild cardiac disease New York Heart Association functional Class I.
Participated in dietary counseling.
Glycosylated hemoglobin greater than or equal to 7.5% and less than 12% at Screening if naïve to oral antidiabetic pharmacologic therapy or taking metformin monotherapy, or greater than or equal to 6.5% and less than 12% if currently taking sulfonylurea monotherapy or taking ulfonylurea/metformin combination therapy.
Stable therapy for cardiovascular dysfunction, defined as no change in therapy for greater than or equal to 4 weeks prior to Randomization.
Exclusion Criteria:
Within the past 30 days treated with rosiglitazone, pioglitazone, or troglitazone or those previously treated with rosiglitazone, pioglitazone, or troglitazone but discontinued from therapy because of lack of efficacy or clinical or laboratory signs of intolerance.
Treated with a sulfonylurea but discontinued for lack of efficacy or clinical or laboratory intolerance.
Currently taking insulin or on continuous insulin therapy for control of their diabetes
Type 1 (insulin-dependent) diabetes mellitus or a history of ketoacidosis.
Any other investigational drug during the 30 days prior to Visit 1 or who will receive such a drug during the time-frame of this study.
History of chronic alcoholism or drug abuse during the 6 months prior to the study.
New York Heart Association functional Class II, III, or IV cardiac disease at Screening, or previous history of Class III or IV.
Any of the following:
myocardial infarction
coronary angioplasty or bypass graft
unstable angina pectoris
transient ischemic attacks
documented cerebrovascular accident. 9. Abdominal, thoracic, or vascular surgery during the 3 months prior to Visit 1.
Planned surgical or catheterization intervention within 6 months following Visit 1.
Awaiting cardiac transplantation.
Intercurrent illness severe enough to require hospitalization during the 3 weeks prior to Visit 1.
Body mass index greater than 48 kg/m2 as calculated by [weight (kg)/height (m)2].
Anemia having hemoglobin less than 10.5 g per dL for men and 10.0 g per dL for women.
Triglyceride level greater than 500 mg per dL.
Clinical evidence of active liver disease or alanine transaminase levels greater than 2.5 times the upper limit of normal.
Serum creatinine greater than 2.0 mg per dL for men and 1.8 mg per dL for women or urinalysis protein (albumin) excretion levels greater than 2 plus on Combistix or equivalent and on repeat 24-hour results with greater than 3 g macroproteinuria.
Unstable coronary syndromes.
Systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg at Screening.
Serious uncontrolled cardiac rhythm disturbances.
Symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm Hg.
Severe, advanced peripheral vascular disease (limb-threatening ischemia) or claudication resulting in the inability to walk greater than 1 block or to climb 10 stairs without interruption.
Lower extremity amputation that would prevent the patient from performing the exercise test.
Any other serious disease or condition which might affect life-expectancy or make it difficult to successfully manage and follow the subjects according to the protocol.
Unexplained clinically significant findings on chest x-ray.
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:
Oral, injected, or inhaled corticosteroids of greater than 2 week duration, or the need for recurrent us of corticosteroids.
Prescription niacin
Anti-diabetic medications except metformin
Cardiovascular medications must remain stable for at least 4 weeks prior to Randomization
Non-steroidal anti-inflammatory drugs
Aspirin greater than 325 mg per day
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
VP Clinical Science Strategy
Organizational Affiliation
Takeda Global Research and Developmnet Center Inc
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
20557330
Citation
Giles TD, Elkayam U, Bhattacharya M, Perez A, Miller AB. Comparison of pioglitazone vs glyburide in early heart failure: insights from a randomized controlled study of patients with type 2 diabetes and mild cardiac disease. Congest Heart Fail. 2010 May-Jun;16(3):111-7. doi: 10.1111/j.1751-7133.2010.00154.x.
Results Reference
result
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Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
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