Study to Compare Pioglitazone and Rosiglitazone in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia

NCT ID: NCT00331487

Last Updated: 2012-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 719 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-09-30
• Study Completion Date: 2004-03-31

Brief Summary

Efficacy comparison of Pioglitazone, once daily (QD), to Rosiglitazone in participants with Type 2 Diabetes

Detailed Description

At least two metabolic defects contribute to the development of type 2 diabetes mellitus: relative insulin insufficiency and insulin resistance. The majority of patients with type 2 diabetes mellitus demonstrate some degree of insulin resistance. Even in the absence of hyperglycemia (high blood sugar), insulin resistance is associated with a cluster of metabolic abnormalities that increase the risk for cardiovascular disease, including dyslipidemia (unhealthy blood fat), increased expression of inflammatory markers, activation of pro-coagulants (pro-clotting), hemodynamic changes, and endothelial dysfunction.

The dyslipidemia associated with insulin resistance and type 2 diabetes mellitus is characterized by elevated triglyceride levels and decreased high-density lipoprotein (good) cholesterol levels. Although low-density lipoprotein (bad) cholesterol levels may not be significantly elevated in patients with type 2 diabetes mellitus, an increase in the proportion of small, dense low-density lipoprotein cholesterol particles of increased atherogenicity (increased formation of lipid deposits in the arteries) is observed. When compared with individuals without type 2 diabetes mellitus, the risk of cardiovascular disease is 2- to 4-fold greater in patients with type 2 diabetes mellitus, and the dyslipidemia of diabetes is an important contributor to the increased risk in this population.

By targeting the insulin resistance underlying type 2 diabetes mellitus, the thiazolidinedione class of oral antihyperglycemic medications possesses both a glucose-lowering effect and the potential to alter lipid/lipoprotein metabolism. Two thiazolidinediones are currently available for the treatment of type 2 diabetes mellitus: pioglitazone hydrochloride (ACTOS, Takeda Pharmaceuticals North America, Inc, Lincolnshire, IL) and rosiglitazone maleate (Avandia, GlaxoSmithKline, Research Triangle Park, NC).

The purpose of this study is to evaluate the triglyceride-lowering effects of pioglitazone to rosiglitazone in patients with type 2 diabetes mellitus and dyslipidemia who are not receiving any other glucose- or lipid-lowering therapies at the same time as the study medications.

Individuals who participate in this study will provide written informed consent and will be required to commit to a screening visit and approximately 7 additional visits at the study center. Study participation is anticipated to be about 39 weeks (or approximately 8 months). Multiple procedures will occur at each visit which may include fasting, blood collection, physical examinations and electrocardiograms. Participants will be required to follow a diabetic diet, self-monitor their blood glucose and maintain a study diary for the duration of the study.

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pioglitazone QD

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

Pioglitazone 30 mg capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks; increasing to pioglitazone 45 mg, capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks

Rosiglitazone QD

Group Type: ACTIVE_COMPARATOR

Rosiglitazone

Intervention Type: DRUG

Rosiglitazone 4 mg capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks; increasing to rosiglitazone 4 mg, capsules, orally, twice daily for up to 12 weeks

Interventions

Pioglitazone

Pioglitazone 30 mg capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks; increasing to pioglitazone 45 mg, capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks

Intervention Type: DRUG

Rosiglitazone

Rosiglitazone 4 mg capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks; increasing to rosiglitazone 4 mg, capsules, orally, twice daily for up to 12 weeks

Intervention Type: DRUG

Other Intervention Names

Actos; AD4833

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus according to the World Health Organization criteria and have diabetes-associated dyslipidemia (fasting triglycerides level between greater than or equal to 150 mg per dL and less than or equal to 600 mg per dL, and a fasting direct low-density lipoprotein cholesterol less than or equal to 130 mg per dL).
• Fasting serum C-peptide greater than or equal to1 ng per
• Glycosylated hemoglobin greater than or equal to 7% and less than or equal to 11% if naive to oral antihyperglycemic medications, or greater than or equal to 9.5% if previously treated with oral antihyperglycemic monotherapy

Exclusion Criteria

• Investigator site personnel and their immediate families. Immediate family defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Treatment with a drug within 30 days of Visit 1 that had not received regulatory approval.
• Treatment within 60 days of Visit 1 with any of the following:

• insulin
• systemic glucocorticoid therapy (excluding topical and inhaled preparations)
• combination glycemic therapy (two or more oral anti-diabetes medications)
• any lipid-lowering agent (including nicotinic acid, fibrates, bile acid resin binders, statins, d thyroxine or neomycin)
• any weight loss agent (prescription or over the counter)
• Pregnant, breast feeding, or intending to become pregnant during the study.
• Serum creatinine greater than or equal to 176.8 μmol per L or greater than or equal to 2 plus per dipstick.
• Proteinuria at Visit 1.
• Alanine transaminase or aspartate transaminase greater than or equal to 1.5 times the upper limit of normal at Visit 1 or had significant clinical signs or symptoms of liver disease.
• History of signs or symptoms of liver disease, such as jaundice or alanine transaminase greater than or equal to 1.5 times the upper limit of normal, while treated with any thiazolidinedione
• Hemoglobin less than 10.5 g per dL for females and less than11.5 g per dL for males at Visit 1.
• Clinically or biochemically based on thyroid stimulating hormone at Visit 1 hypothyroid or hyperthyroid.
• History of myocardial infarction, acute cardiovascular event, or heart surgery within 6 months of Visit 1.
• Functional New York Heart Association Cardiac Class III or IV disease.
• Receiving renal dialysis or has had received a renal transplant.
• Undergoing therapy for a malignancy other than basal cell or squamous cell skin cancer.
• Clinical signs or symptoms of drug or alcohol abuse.
• History of HIV infection.
• Allergy to any glitazone drug.
• Medical history or the presence of any clinically significant or unstable medical condition that made the patient unlikely to complete the study.
• Any condition or situations that precluded adherence and completion of the protocol or a precluding ability to voluntarily give informed consent.

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfonso Perez, MD

Role: STUDY_DIRECTOR

Takeda

Locations

Anniston, Alabama, United States

Birmingham, Alabama, United States

Tucson, Arizona, United States

Concord, California, United States

Fremont, California, United States

Los Angeles, California, United States

Palos Verdes Estates, California, United States

San Diego, California, United States

Santa Barbara, California, United States

Santa Rosa, California, United States

Aurora, Colorado, United States

Englewood, Colorado, United States

Avon, Connecticut, United States

Hamden, Connecticut, United States

Longwood, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Atlanta, Georgia, United States

Fayetteville, Georgia, United States

Honolulu, Hawaii, United States

Idaho Falls, Idaho, United States

Chicago, Illinois, United States

Indianapolis, Indiana, United States

South Bend, Indiana, United States

New Orleans, Louisiana, United States

Baltimore, Maryland, United States

Frederick, Maryland, United States

Salisbury, Massachusetts, United States

South Yarmouth, Massachusetts, United States

Waltham, Massachusetts, United States

Minneapolis, Minnesota, United States

Chesterfield, Missouri, United States

Omaha, Nebraska, United States

East Setauket, New York, United States

Endwell, New York, United States

New York, New York, United States

Rochester, New York, United States

Staten Island, New York, United States

Charlotte, North Carolina, United States

Durham, North Carolina, United States

Greenville, North Carolina, United States

Morehead City, North Carolina, United States

Wilmington, North Carolina, United States

Columbus, Ohio, United States

Franklin, Ohio, United States

Tulsa, Oklahoma, United States

Portland, Oregon, United States

Salem, Oregon, United States

Philadelphia, Pennsylvania, United States

Pottstown, Pennsylvania, United States

Providence, Rhode Island, United States

Mt. Pleasant, South Carolina, United States

Knoxville, Tennessee, United States

Memphis, Tennessee, United States

Beaumont, Texas, United States

Conroe, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Lake Jackson, Texas, United States

San Antonio, Texas, United States

Ogden, Utah, United States

Mechanicsville, Virginia, United States

Newport News, Virginia, United States

Virginia Beach, Virginia, United States

Federal Way, Washington, United States

Wenatchee, Washington, United States

Milwaukee, Wisconsin, United States

Countries

United States

References

Goldberg RB, Kendall DM, Deeg MA, Buse JB, Zagar AJ, Pinaire JA, Tan MH, Khan MA, Perez AT, Jacober SJ; GLAI Study Investigators. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005 Jul;28(7):1547-54. doi: 10.2337/diacare.28.7.1547.

Reference Type: RESULT

PMID: 15983299 (View on PubMed)

Tilden DP, Mariz S, O'Bryan-Tear G, Bottomley J, Diamantopoulos A. A lifetime modelled economic evaluation comparing pioglitazone and rosiglitazone for the treatment of type 2 diabetes mellitus in the UK. Pharmacoeconomics. 2007;25(1):39-54. doi: 10.2165/00019053-200725010-00005.

Reference Type: RESULT

PMID: 17192117 (View on PubMed)

Deeg MA, Buse JB, Goldberg RB, Kendall DM, Zagar AJ, Jacober SJ, Khan MA, Perez AT, Tan MH; GLAI Study Investigators. Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2007 Oct;30(10):2458-64. doi: 10.2337/dc06-1903. Epub 2007 Jun 26.

Reference Type: RESULT

PMID: 17595355 (View on PubMed)

Related Links

http://general.takedapharm.com/content/file/pi.pdf?applicationcode=ab2d7112-8eb3-465a-8fda-35018a9eafb0&fileTypeCode=ACTOSPI

ACTOS® Package Insert

Other Identifiers

U1111-1115-9039

Identifier Type: REGISTRY

Identifier Source: secondary_id

H6E-US-GLAI

Identifier Type: -

Identifier Source: org_study_id