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Diabetes MellitusPhase 3CHICAGONCT00225264

Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.

A Phase 3 study testing Pioglitazone and Glimepiride in people with Diabetes Mellitus, run by Takeda at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary purpose of this study is to compare the effects of pioglitazone, once daily (QD), versus glimepiride on the amount of thickening of the carotid artery. Read more about this study

Who is it for?
Ages 45 to 85 years
Conditions the study is for
Diabetes Mellitus
What is being tested?
Pioglitazone and Glimepiride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
458 participants
Where
1 siteUnited States
Study dates
Oct 2003to May 2006
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 45 to 85 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. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to the time of randomization.
  • Diagnosis of type 2 diabetes mellitus.
  • Has received appropriate counseling on lifestyle modification for type 2 diabetes, including diet and exercise.
  • Naïve to or not currently taking antidiabetic therapy, or is currently treated with monotherapy or combination antidiabetic therapy.
  • Glycosylated hemoglobin greater than or equal to 6.0% and less than 9% at screening if taking antidiabetic medication or glycosylated hemoglobin greater than or equal to 6.5% and less than 10% at screening if naïve to or not taking antidiabetic medication.

Who cannot join

  • Type 1 diabetes mellitus.
  • Taking more than 2 antidiabetic therapies at screening. For combination medications, each component is counted as 1 therapy.
  • Symptomatic coronary artery disease, cerebrovascular disease, or peripheral vascular disease at the time of screening.
  • Taking or have taken pioglitazone or other thiazolidinediones within 12 weeks of randomization or were discontinued from thiazolidinedione therapy due to lack of efficacy or clinical or laboratory signs of intolerance.
  • Was discontinued from glimepiride or other sulfonylureas due to lack of efficacy or clinical or laboratory signs of intolerance.
  • Participating in another investigational study or has participated in an investigational study within the past 30 days or is scheduled to participate in an investigational study during the time frame of this study.
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  • Women who are pregnant, intend to become pregnant during the course of the study, or are lactating.
  • Men who have serum creatinine greater than or equal to 2.0 mg/dL (greater than or equal to 1.5 mg/dL if taking metformin) and women with serum creatinine greater than or equal to 1.8 mg/dL (greater than or equal to1.4 mg/dL if taking metformin).
  • Unexplained microscopic hematuria of greater than plus 1 confirmed by repeat testing.
  • History of drug abuse or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
  • Clinical cardiac failure as defined by New York Heart Association class III or IV, or known left ventricular dysfunction measured as left ventricular ejection fraction less than 40%, or by current use of diuretics or angiotensin converting enzyme inhibitors for the treatment of heart failure. Use of these agents for other therapeutic reasons is not an exclusion.
  • Alanine transaminase level of greater than 2.5 times the upper limit of normal, active liver disease or jaundice.
  • Weighs greater than 300 pounds or has a body mass index greater than 45 kg/m2 as calculated by weight (kg)/height (m)2 or weight (pounds)/height (inches)2 x 703.
  • Has taken excluded medications.
  • Known or suspected malignancy or recurrence of malignancy within the past 5 years, with the exception of basal cell carcinoma and Stage 1 squamous cell carcinoma of the skin.
  • Any disease where, in the opinion of the investigator, survival is expected to be less than 18 months.
  • Anticipated to undergo coronary bypass surgery or cardiac intervention during the course of the study.
  • Has, in the opinion of the investigator, clinically significant valvular heart disease likely to require surgical repair or replacement during the course of the study.
  • Has had uncontrolled hypertension (ie, sitting systolic blood pressure greater than160 mm Hg or sitting diastolic blood pressure greater than 100 mm Hg) at randomization.
  • Men who have hemoglobin less than10.5 g/dL and women who have hemoglobin less than10.0 g/dL.
  • Triglycerides greater than 500 mg/dL.
  • Unwilling or unable to comply with the protocol or scheduled appointments.
  • Unable to understand verbal and/or written English or any other language for which a certified translation of the informed consent is available.
  • Known or suspected hypersensitivity to blood, blood products, or albumin.
  • Subjects for whom it is not possible to obtain good quality images of the common carotid artery for technical reasons.
  • Potentially clinically significant stenosis of the carotid artery as determined according to current guidelines by the physician assessing carotid intima-media thickness results. In these cases, the carotid intima-media thickness results should be reviewed by the investigator in consultation with the carotid intima-media thickness physician prior to determining whether the subject should be randomized.
  • Has had bilateral endarterectomies, bilateral carotid stents, or radiation to the head or neck.
  • Has received radiation therapy in the past year, who has had more than one computed tomography scan in the past year, or who is unable to raise one's arms above one's head while in a prone position.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Study site

    Chicago, Illinois

Other trials in United States

About this study

Official title: A Double-Blind, Randomized, Comparator-Controlled Study in Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl Versus Glimepiride on the Rate of Progression of Atherosclerotic Disease as Measured by Carotid Intima-Media Thickness

The primary purpose of this study is to compare the effects of pioglitazone, once daily (QD), versus glimepiride on the amount of thickening of the carotid artery.

Read the detailed description

Diabetes is a chronic disease with multiple metabolic defects that result in hyperglycemia arising from inadequate insulin activity. Type 2 diabetes usually is the result of a progression from reduced sensitivity of hepatic and peripheral tissue cells to circulating insulin to a progressive inability of the body to produce adequate insulin to overcome insulin resistance, resulting in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 21 million people have diabetes, with type 2 diabetes occurring in approximately 90% to 95% of cases.

Type 2 diabetes also represents an important risk group for the development of accelerated atherosclerosis. Atherosclerosis can be measured with different procedures. One of the noninvasive, commonly used procedures is carotid B-mode ultrasound measurement of carotid intima-media thickness, which has been shown to be a useful measurement for clinical cardiovascular events in multiple studies.

Coronary artery calcification is a marker of coronary artery disease, and electron beam tomography is a sensitive tool for evaluation of coronary artery calcium. Electron beam tomography measurements produce a coronary artery calcium score that represents plaque burden. Subjects with diabetes mellitus have accelerated coronary artery disease. Even after treatment of elevated lipid levels, rates for coronary events still exceed those seen in non-diabetic subjects treated with the same lipid-lowering agents. Diabetic subjects also continue to have increased mortality rates compared with non-diabetic subjects after a myocardial infarction. Therefore, detection of sub-clinical atherosclerosis and prevention of myocardial infarction in subjects with diabetes remains an important priority.

Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd, and depends on the presence of insulin for its mechanism of action. Data suggests that thiazolidinediones may inhibit the development of atherosclerosis in non-diabetic, atherosclerosis mouse models. These findings suggest that this class of drugs may have an effect on vessel walls to suppress development of atherosclerotic lesions.

This study will investigate the effects of pioglitazone and glimepiride on the rate of progression of atherosclerotic disease as measured by carotid intima-media thickness and by electron beam tomography of the coronary arteries in subjects with type 2 diabetes.

Being tested
Pioglitazone, Glimepiride
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, AD-4833

    Pioglitazone 15 mg titrated up to 45 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily for up to 72 weeks.

  • GlimepirideDrug

    Also called Amaryl

    Pioglitazone placebo-matching tablets, orally, once daily and glimepiride 1 mg titrated up to 4 mg, capsules, orally, once daily for up to 72 weeks.

Study groups in NCT00225264
Study groupRoleWhat they receive
Pioglitazone QDExperimentalNot described
Receives: Drug: Pioglitazone
Glimepiride QDActive comparatorNot described
Receives: Drug: Glimepiride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute change from Baseline in carotid intima-media thickness.

    Measured: Weeks 24, 48 and Final Visit.

Secondary outcomes (5)
  1. Change from Baseline in carotid intima-media thickness.

    Measured: Weeks 24, 48 and Final Visit.

  2. Change from Baseline in coronary artery calcium-volume score.

    Measured: At Final Visit

  3. Change from Baseline in abdominal adipose tissue content and distribution.

    Measured: At Final Visit

  4. Incidence of cardiovascular events as a composite of cardiovascular mortality, nonfatal myocardial infarction and nonfatal stroke

    Measured: At each occurrence

  5. Incidence of cardiovascular events as a composite of cardiovascular mortality, nonfatal MI, nonfatal stroke, coronary revascularization, carotid endarterectomy/stenting, hospitalization for unstable angina and hospitalization for CHF

    Measured: At each occurrence

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2005 (estimated)
  2. Study startOct 2003
  3. Primary completionMay 2006
  4. Study completionMay 2006

Resources

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
458 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00225264
Sponsor's protocol ID
01-02-TL-OPI-518
Other IDs
U1111-1114-2799
Acronym
CHICAGO
Status last verified
Feb 2012
First submitted
21 Sep 2005
Last updated
28 Feb 2012
Results posted
No
Data monitoring committee
No

Publications

  • Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D'Agostino RB Sr, Perez A, Provost JC, Haffner SM. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006 Dec 6;296(21):2572-81. doi: 10.1001/jama.296.21.joc60158. Epub 2006 Nov 13.

    PubMed 17101640
  • Davidson M, Meyer PM, Haffner S, Feinstein S, D'Agostino R Sr, Kondos GT, Perez A, Chen Z, Mazzone T. Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation. 2008 Apr 22;117(16):2123-30. doi: 10.1161/CIRCULATIONAHA.107.746610. Epub 2008 Apr 14.

    PubMed 18413496
  • Sam S, Haffner S, Davidson MH, D'Agostino RB Sr, Feinstein S, Kondos G, Perez A, Mazzone T. Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes. Diabetes. 2008 Aug;57(8):2022-7. doi: 10.2337/db08-0157. Epub 2008 May 9.

    PubMed 18469202
  • Mazzone T, Meyer PM, Kondos GT, Davidson MH, Feinstein SB, D'Agostino RB Sr, Perez A, Haffner SM. Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes. Diabetes. 2007 Mar;56(3):849-55. doi: 10.2337/db06-0935.

    PubMed 17327456
  • Sam S, Haffner S, Davidson MH, D'Agostino RB Sr, Feinstein S, Kondos G, Perez A, Mazzone T. Relation of abdominal fat depots to systemic markers of inflammation in type 2 diabetes. Diabetes Care. 2009 May;32(5):932-7. doi: 10.2337/dc08-1856. Epub 2009 Feb 19.

    PubMed 19228869
  • Betteridge DJ. CHICAGO, PERISCOPE and PROactive: CV risk modification in diabetes with pioglitazone. Fundam Clin Pharmacol. 2009 Dec;23(6):675-9. doi: 10.1111/j.1472-8206.2009.00741.x. Epub 2009 Sep 10.

    PubMed 19744248

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pioglitazone and Glimepiride in people with Diabetes Mellitus, run by Takeda at 1 site in United States.

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 5 inclusion and 28 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.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Absolute change from Baseline in carotid intima-media thickness. (time frame: Weeks 24, 48 and 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 NCT00225264, which also lists 6 linked publications.

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.

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