Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus

NCT00225277 | Completed Phase 3 Results

• 2 other identifiers: 01-01-TL-OPI-516U1111-1114-0400
• Study Type: interventional
• Target: 547
• Locations: 4 countries
• Sites: 79

Brief Summary

The purpose of this study was to determine the efficacy of pioglitazone, once daily (QD), compared to glimepiride on atherosclerotic disease measured by intravascular ultrasound.

Conditions

Diabetes Mellitus

Keywords

Glucose Metabolism Disorder; Dysmetabolic Syndrome; Type II Diabetes; Diabetes Mellitus, Lipoatrophic; Dyslipidemia; Drug Therapy; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Nominal Change From Baseline in Percent Atheroma Volume

  The nominal change from baseline in percent atheroma volume for all slices of anatomically comparable segments of the target coronary artery. Assessment completed at the Week 72 visit or Final Visit if treatment was prematurely discontinued.

  Baseline and Final Visit (up to 72 weeks)

Secondary Outcomes (4)

• Nominal Change From Baseline in Normalized Total Atheroma Volume

  Baseline and Final Visit (up to 72 weeks)

• Number of Subjects Experiencing Any of the Composite Endpoint A Cardiovascular Events

  Up to 72 weeks

• Number of Subjects Experiencing Any of the Composite Endpoint B Cardiovascular Events

  Up to 72 weeks

• Number of Subjects Experiencing Any of the Composite Endpoint C Cardiovascular Events

  Up to 72 weeks

Other Outcomes (1)

• Number of Cardiovascular Events as Adjudicated by the Clinical Endpoint Committee

  Up to 72 weeks

Study Arms (2)

Pioglitazone QD

EXPERIMENTAL

Drug: Pioglitazone

Glimepiride QD

ACTIVE COMPARATOR

Drug: Glimepiride

Interventions

Pioglitazone DRUG

Up to 45 mg pioglitazone (optimized for glucose control), tablets, orally, once daily for up to 72 weeks.

Also known as: ACTOS®, AD4833

Pioglitazone QD

Glimepiride DRUG

Up to 4 mg of glimepiride (optimized for glucose control), tablets, orally, once daily for up to 72 weeks.

Glimepiride QD

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females of childbearing potential who were sexually active agreed to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
• Had a diagnosis of type 2 diabetes mellitus
• Have received appropriate counseling on lifestyle modification for type 2 diabetes, including diet and exercise.
• naïve to or was not currently taking antidiabetic therapy, or were currently treated with monotherapy or combination therapy.
• Had a glycosylated hemoglobin level greater than or equal to 6.0% and less than 9% at screening if taking antidiabetic medication or greater than or equal to 6.5% and less than 10% at screening if naive to or not taking antidiabetic medication.
• Angiographic criteria:
• Entire Coronary Circulation: must have angiographic evidence of coronary heart disease as defined by at least 1 lesion in a native coronary artery that has greater than or equal to 20% reduction in lumen diameter by angiographic visual estimation.
• Left Main Coronary Artery: must not have greater than 50% reduction in lumen diameter by visual angiographic estimation.
• Target Coronary Artery:
• The target vessel, which includes the main artery and all of its side branches, had not undergone prior percutaneous coronary intervention or coronary artery bypass graft surgery.
• The target vessel, which includes the main artery and all of its side branches, was not currently a candidate for intervention or a likely candidate for intervention over the next 72 weeks.
• The target vessel was not a bypass graft.
• The target vessel was not infarct related.
• Had previous coronary artery bypass surgery at least six weeks prior to the qualifying intravascular ultrasound are eligible provided they are stable and meet all other entry criteria.
• Had an intravascular ultrasound tape deemed to be of acceptable intravascular ultrasound image quality and demonstrated adherence to the intravascular ultrasound interrogation protocol, as determined by the intravascular ultrasound Core Laboratory™ assessment.

You may not qualify if:

• Had type I diabetes mellitus.
• Had participated in another investigational study, or participated in an investigational study 30 days prior to the start of this study, or who were scheduled to participate in an investigational study during the time frame of this study.
• Male subjects who had a serum creatinine level greater than or equal to 2.0 mg/dL (greater than or equal to 177 µmol/L) (greater than or equal to 1.5 mg/dL; \[greater than or equal to 133 µmol /L\] if taking metformin) and female subjects who have serum creatinine greater than or equal to 1.8 mg/dL \[greater than or equal to 159 µmol /L\] (greater than or equal to 1.4 mg/dL \[greater than or equal to 124 µmol /L\] if taking metformin).
• Had unexplained microscopic hematuria greater than +1, confirmed by repeat testing.
• Had a 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.
• Had 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 treatment of heart failure.
• Had an alanine transaminase level of greater than 2.5 times the upper limit of normal active liver disease, or jaundice.
• Had a body mass index greater than 48 kg/m2 as calculated by weight (kg)/height (m2) or weight (pounds)/height (inches) 2 x 703.
• Was required to take or intended to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may have interfered with evaluation of the study medication, including:
• Chronically used oral glucocorticoids (eg, prednisone, cortisone, hydrocortisone, dexamethasone)
• Niacin greater than100 mg a day, including niacin-containing products such as Advicor®
• Chronically used steroid-joint injections
• Thiazolidinediones
• Sulfonylureas
• Metformin/sulfonylurea combination

Sponsors & Collaborators

• Takeda: lead

Study Sites (79)

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Huntington Beach, California, United States

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Los Angeles, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Torrance, California, United States

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Bridgeport, Connecticut, United States

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Farmington, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Bay Pines, Florida, United States

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Jacksonville, Florida, United States

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Decatur, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Edgewood, Kentucky, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Bangor, Maine, United States

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Baltimore, Maryland, United States

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Detroit, Michigan, United States

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Flint, Michigan, United States

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Kalamazoo, Michigan, United States

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Petoskey, Michigan, United States

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Pontiac, Michigan, United States

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Royal Oak, Michigan, United States

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Ypsilanti, Michigan, United States

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Duluth, Minnesota, United States

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Minneapolis, Minnesota, United States

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Saint Cloud, Minnesota, United States

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Columbia, Missouri, United States

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Camden, New Jersey, United States

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Albany, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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The Bronx, New York, United States

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Troy, New York, United States

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West Islip, New York, United States

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Williamsville, New York, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Westlake, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Abington, Pennsylvania, United States

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Bryn Mawr, Pennsylvania, United States

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Hershey, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Providence, Rhode Island, United States

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Greenville, South Carolina, United States

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Memphis, Tennessee, United States

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Oak Ridge, Tennessee, United States

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Amarillo, Texas, United States

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Houston, Texas, United States

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Lubbock, Texas, United States

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San Antonio, Texas, United States

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Charlottesville, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Everett, Washington, United States

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Green Bay, Wisconsin, United States

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Ciudad de Buenos Aires, Argentina

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Córdoba, Argentina

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Quilmes, Argentina

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Winnepeg, Manitoba, Canada

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Saint John, New Brunswick, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Montreal, Quebec, Canada

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Sainte-Foy, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Santiago, Chile

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Related Publications (3)

• Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, Jure H, De Larochelliere R, Staniloae CS, Mavromatis K, Saw J, Hu B, Lincoff AM, Tuzcu EM; PERISCOPE Investigators. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008 Apr 2;299(13):1561-73. doi: 10.1001/jama.299.13.1561. Epub 2008 Mar 31.

  PMID: 18378631 RESULT

• 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.

  PMID: 19744248 RESULT

• Nicholls SJ, Tuzcu EM, Wolski K, Bayturan O, Lavoie A, Uno K, Kupfer S, Perez A, Nesto R, Nissen SE. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. J Am Coll Cardiol. 2011 Jan 11;57(2):153-9. doi: 10.1016/j.jacc.2010.06.055.

  PMID: 21211686 RESULT

Related Links

• ACTOS® Package Insert

MeSH Terms

Conditions

Diabetes Mellitus; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus, Lipoatrophic; Dyslipidemias; Atherosclerosis

Interventions

Pioglitazone; glimepiride

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Composite Endpoints A,B,C include cardiovascular mortality, nonfatal MI and nonfatal stroke. In addition, B: coronary revascularization, carotid endarterectomy/stenting, unstable angina hosp. or CHF; C: hospitalization for unstable angina or CHF.

Results Point of Contact

• Title: Sr. VP Clinical Sciences
• Organization: Takeda Global Research and Development Center Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• VP Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2005
• First Posted: September 23, 2005
• Study Start: July 1, 2003
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: February 28, 2012
• Results First Posted: June 10, 2009

Record last verified: 2012-02

Locations

AR (3); CA (10); US (65); CL (1)