Diabetes MellitusPhase 3NCT00521742
Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
A Phase 3 study testing Pioglitazone and Glyburide in people with Diabetes Mellitus, run by Takeda.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Pioglitazone and Glyburide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- Mar 2001to Jan 2003
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 36Show fewer
- 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
About this study
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)
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.
Read the 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.
- Conditions
- Diabetes Mellitus
- Being tested
- Pioglitazone, Glyburide
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
- Medical subject headings
- Diabetes Mellitus, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Diabetes Mellitus, Lipoatrophic, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos, AD4833
Pioglitazone 15 mg to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 52 weeks.
GlyburideDrug
Glyburide 2.5 mg to 15 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks.
PioglitazoneDrug
Also called Actos, AD4833
Pioglitazone 15 mg or 30 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally once daily for up to 52 weeks.
GlyburideDrug
Glyburide 5 mg or 10 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally once daily for up to 52 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone 15 mg to 45 mg QD | Experimental | Not described Receives: Drug: Pioglitazone |
| Glyburide 2.5 mg to 15 mg, QD | Active comparator | Not described Receives: Drug: Glyburide |
| Pioglitazone 15 mg or 30 mg QD | Experimental | Not described Receives: Drug: Pioglitazone |
| Glyburide 5 mg or 10 mg, QD | Active comparator | Not described Receives: Drug: Glyburide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the walking distance during a standardized 6-minute walk test.
Measured: Weeks 2, 16, 24, 40, and 52 or Final Visit
Secondary outcomes (10)
Morbidity and Mortality Due to Cardiovascular Events.
Measured: At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit
Change in Cardiovascular Treatment Program.
Measured: At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit
Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate)
Measured: Weeks 24 and 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass)
Measured: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction)
Measured: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Cardiac Index)
Measured: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Fractional Shortening)
Measured: Week 52 or Final Visit
Change in Blood Pressure
Measured: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
Change in Heart Rate
Measured: Weeks 24 and 52 or Final Visit
Change in Body Weight
Measured: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2007 (estimated)
- Study startMar 2001
- Primary completionJan 2003
- Study completionJan 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Pharmaceuticals North America, Inc.
- Responsible party
- Sponsor
- Investigators
- VP Clinical Science Strategy, Study director, Takeda Global Research and Developmnet Center Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00521742
- Sponsor's protocol ID
- 01-00-TL-OPI-520
- Other IDs
- U1111-1114-1616
- Status last verified
- Feb 2012
- First submitted
- 25 Aug 2007
- Last updated
- 28 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20557330
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00521742
- Acronym / sponsor ID
- 01-00-TL-OPI-520
- Conditions
- Diabetes Mellitus
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Pharmaceuticals North America, Inc.
- Study start
- Mar 2001
- Primary completion
- Jan 2003 (actual)
- Study completion
- Jan 2003 (actual)
- First posted
- 28 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone 15 mg to 45 mg QD | Experimental | Drug: Pioglitazone |
| Glyburide 2.5 mg to 15 mg, QD | Active comparator | Drug: Glyburide |
| Pioglitazone 15 mg or 30 mg QD | Experimental | Drug: Pioglitazone |
| Glyburide 5 mg or 10 mg, QD | Active comparator | Drug: Glyburide |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (36 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: Actos, AD4833Pioglitazone 15 mg to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 52 weeks. | Drug | Pioglitazone 15 mg to 45 mg QD |
| GlyburideGlyburide 2.5 mg to 15 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks. | Drug | Glyburide 2.5 mg to 15 mg, QD |
| PioglitazoneAlso: Actos, AD4833Pioglitazone 15 mg or 30 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally once daily for up to 52 weeks. | Drug | Pioglitazone 15 mg or 30 mg QD |
| GlyburideGlyburide 5 mg or 10 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally once daily for up to 52 weeks. | Drug | Glyburide 5 mg or 10 mg, QD |
Primary outcome
Change in the walking distance during a standardized 6-minute walk test.
Time frame: Weeks 2, 16, 24, 40, and 52 or Final Visit
10 secondary outcomes
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
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
Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate)
Time frame: Weeks 24 and 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass)
Time frame: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction)
Time frame: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Cardiac Index)
Time frame: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Fractional Shortening)
Time frame: Week 52 or Final Visit
Change in Blood Pressure
Time frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
Change in Heart Rate
Time frame: Weeks 24 and 52 or Final Visit
Change in Body Weight
Time frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2012.
- Results publication: PubMed 20557330Giles 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.
- ACTOS® Package InsertLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
VP Clinical Science Strategy study director
Takeda Global Research and Developmnet Center Inc
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pioglitazone and Glyburide in people with Diabetes Mellitus, run by Takeda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the walking distance during a standardized 6-minute walk test. (time frame: Weeks 2, 16, 24, 40, and 52 or Final Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00521742, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2012.