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

Primary Purpose

Diabetes Mellitus

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Rosiglitazone
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

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

35 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pioglitazone QD

Rosiglitazone QD

Arm Description

Outcomes

Primary Outcome Measures

Change in fasting triglyceride level

Secondary Outcome Measures

Change in fasting low-density lipoprotein cholesterol.
Change in fasting high-density lipoprotein cholesterol.
Change in fasting total cholesterol.
Change in fasting free fatty acids.
Change in plasminogen activator inhibitor 1
Change in high-sensitivity C-reactive protein
Change in fasting C-peptide.
Homeostasis model assessment-insulin resistance mode.
Change in fasting insulin.
Homeostasis model assessment-beta cell function.
Change in glycosylated hemoglobin.
Change in fasting plasma glucose.
Low-density lipoprotein particle concentration.
Low-density lipoprotein particle size.
High-density lipoprotein particle size.
Very low-density lipoprotein particle size.
Apolipoprotein A-I.
Apolipoprotein B
Lipoprotein a
Apolipoprotein C-III.

Full Information

First Posted
May 30, 2006
Last Updated
February 27, 2012
Sponsor
Takeda
Collaborators
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00331487
Brief Title
Study to Compare Pioglitazone and Rosiglitazone in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia
Official Title
Pioglitazone Versus Rosiglitazone in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
September 2000 (undefined)
Primary Completion Date
March 2004 (Actual)
Study Completion Date
March 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

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
719 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pioglitazone QD
Arm Type
Experimental
Arm Title
Rosiglitazone QD
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos, AD4833
Intervention Description
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
Intervention Name(s)
Rosiglitazone
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in fasting triglyceride level
Time Frame
Final Visit
Secondary Outcome Measure Information:
Title
Change in fasting low-density lipoprotein cholesterol.
Time Frame
Final Visit
Title
Change in fasting high-density lipoprotein cholesterol.
Time Frame
Final Visit
Title
Change in fasting total cholesterol.
Time Frame
Final Visit
Title
Change in fasting free fatty acids.
Time Frame
Final Visit
Title
Change in plasminogen activator inhibitor 1
Time Frame
Final Visit
Title
Change in high-sensitivity C-reactive protein
Time Frame
Final Visit
Title
Change in fasting C-peptide.
Time Frame
Final Visit
Title
Homeostasis model assessment-insulin resistance mode.
Time Frame
Final Visit
Title
Change in fasting insulin.
Time Frame
Final Visit
Title
Homeostasis model assessment-beta cell function.
Time Frame
Final Visit
Title
Change in glycosylated hemoglobin.
Time Frame
Final Visit
Title
Change in fasting plasma glucose.
Time Frame
Final Visit
Title
Low-density lipoprotein particle concentration.
Time Frame
Final Visit
Title
Low-density lipoprotein particle size.
Time Frame
Final Visit
Title
High-density lipoprotein particle size.
Time Frame
Final Visit
Title
Very low-density lipoprotein particle size.
Time Frame
Final Visit
Title
Apolipoprotein A-I.
Time Frame
Final Visit
Title
Apolipoprotein B
Time Frame
Final Visit
Title
Lipoprotein a
Time Frame
Final Visit
Title
Apolipoprotein C-III.
Time Frame
Final Visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfonso Perez, MD
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35234
Country
United States
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
City
Concord
State/Province
California
ZIP/Postal Code
94520
Country
United States
City
Fremont
State/Province
California
ZIP/Postal Code
94538
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
City
Palos Verdes Estates
State/Province
California
ZIP/Postal Code
90274
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95405
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80110
Country
United States
City
Avon
State/Province
Connecticut
ZIP/Postal Code
06001
Country
United States
City
Hamden
State/Province
Connecticut
ZIP/Postal Code
06518
Country
United States
City
Longwood
State/Province
Florida
ZIP/Postal Code
32750
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
City
Fayetteville
State/Province
Georgia
ZIP/Postal Code
30214
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60610
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70127
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21702
Country
United States
City
Salisbury
State/Province
Massachusetts
ZIP/Postal Code
01952
Country
United States
City
South Yarmouth
State/Province
Massachusetts
ZIP/Postal Code
02664
Country
United States
City
Waltham
State/Province
Massachusetts
ZIP/Postal Code
02453
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
City
Chesterfield
State/Province
Missouri
ZIP/Postal Code
63017
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
City
Endwell
State/Province
New York
ZIP/Postal Code
13760
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14607
Country
United States
City
Staten Island
State/Province
New York
ZIP/Postal Code
10305
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28211
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27713
Country
United States
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28412
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
City
Franklin
State/Province
Ohio
ZIP/Postal Code
45005
Country
United States
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
City
Salem
State/Province
Oregon
ZIP/Postal Code
97302
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19124
Country
United States
City
Pottstown
State/Province
Pennsylvania
ZIP/Postal Code
19464
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
City
Beaumont
State/Province
Texas
ZIP/Postal Code
77701
Country
United States
City
Conroe
State/Province
Texas
ZIP/Postal Code
77384
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
City
Lake Jackson
State/Province
Texas
ZIP/Postal Code
77566
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
City
Ogden
State/Province
Utah
ZIP/Postal Code
84403
Country
United States
City
Mechanicsville
State/Province
Virginia
ZIP/Postal Code
23111
Country
United States
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23606
Country
United States
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23455
Country
United States
City
Federal Way
State/Province
Washington
ZIP/Postal Code
98003
Country
United States
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801
Country
United States
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53209
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15983299
Citation
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.
Results Reference
result
PubMed Identifier
17192117
Citation
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. Erratum In: Pharmacoeconomics. 2007;25(3):237.
Results Reference
result
PubMed Identifier
17595355
Citation
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.
Results Reference
result

Learn more about this trial

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

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