Clinical trial NCT00672919: Pioglitazone Study of Triglyceride Changes in Subjects With Type 2 Diabetes After Conversion From Rosiglitazone.
Official title: A Single-Arm, Open-Label, Multicenter Study Evaluating the Triglyceride Changes in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia Following Treatment Conversion From Rosiglitazone to Pioglitazone HCl in Combination With Stable Statin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus
Keywords: Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-05-06
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the triglyceride changes in subjects with type 2 diabetes mellitus taking pioglitazone, once daily (QD), following treatment conversion from rosiglitazone.

Detailed description: Diabetes mellitus is a chronic disease with multiple metabolic defects that result in hyperglycemia arising from inadequate insulin activity. Type 2 diabetes has a genetic predisposition, but lifestyle, physical habits and age play important roles in determining its time of onset and severity. Type 2 diabetes is usually the result of a progression from reduced sensitivity of hepatic (liver) and peripheral-tissue cells to circulating insulin (ie, insulin resistance) to a progressive inability of the body to produce adequate insulin to overcome insulin resistance (ie, insulin deficiency due to beta-cell insufficiency) resulting in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 15.7 million people have diabetes, with type 2 diabetes occurring in approximately 90 to 95% of cases.

Therapeutic agents have been developed to address each of the major functional metabolic defects associated with type 2 diabetes. Recently introduced drugs for diabetes therapy are the thiazolidinedione class. Thiazolidinediones increase glucose utilization, decrease gluconeogenesis and increase glucose disposal through an incompletely understood mechanism but one associated with binding of the drug to receptors known as peroxisomal proliferator-activated receptors.

Thiazolidinediones are peroxisomal proliferator-activated receptor agonists reducing insulin resistance in muscle cells, adipose (fat) tissue, and hepatic cells (inhibiting hepatic gluconeogenesis) with no direct impact on insulin secretion. Thus peroxisomal proliferator-activated receptor agonists improve glycemic control and result in reduced levels of circulating insulin. Peroxisomal proliferator-activated receptors are found in various tissues important for insulin action, with the greatest concentration of these receptors is in adipose tissue.

Pioglitazone is a peroxisomal proliferator-activated receptor agonist developed by Takeda Chemical Industries, Ltd. (Osaka, Japan).

Participation in this study is anticipated to be approximately 20 weeks.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with type 2 diabetes mellitus
* 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
* Has been taking a stable dose of rosiglitazone for greater than 90 days prior to screening.
* Has a triglyceride level greater than 200 mg per dL but less than 1000 mg per dL.
* Has been taking a stable statin therapy for greater than 90 days prior to screening.
* Has a glycosylated hemoglobin less than 10.5%.

Exclusion Criteria:

* Type 1 diabetes mellitus.
* Treated with Gemfibrozil within 90 days of screening.
* Previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug.
* The subject has an alanine aminotransaminase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
* Male subjects who have serum creatinine greater than 2.0 mg per dL and female subjects with serum creatinine greater than1.8 mg per dL.
* Unexplained microscopic hematuria greater than plus 1 confirmed by repeat testing.
* Male subjects who have hemoglobin less than 10.5 g per dL and female subjects who have hemoglobin less than 10.0 g per dL.
* Significant cardiovascular disease including, but not limited to, New York Heart Association Functional (Cardiac) Classification III or IV
* Currently is participating in another investigational study or has participated in an investigational study within the past 30 days.
* Any other serious disease or condition that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol.
* Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  * Glucocorticoids (eg. prednisone, cortisone, hydrocortisone, dexamethasone) with the exception of a topical glucocorticoid agent.
  * Gemfibrozil
  * Steroid-joint injections.
  * Thiazolidinediones with the exception of the study medication.

Primary outcomes:
measure: Change from Baseline in Triglyceride Levels
timeFrame: Weeks 8 and 17 or Final Visit
Secondary outcomes:
measure: Change from Baseline in Total Cholesterol
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in direct Low Density Lipoprotein cholesterol
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in High Density Lipoprotein cholesterol
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in apolipoprotein B (apoB)
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in apolipoprotein A1 (apoA1)
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in Free Fatty Acids
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in Lipid Fractionation
timeFrame: Weeks 8 and 17 or Final Visit
measure: Change from Baseline in C-reactive Protein
timeFrame: Weeks 8 and 17 or Final Visit
Other outcomes:
Locations:
city: Birmingham,
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Bellflower
country: United States
state: California
city: Burlingame
country: United States
state: California
city: Fresno,
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Norwalk
country: United States
state: Connecticut
city: Waterbury
country: United States
state: Connecticut
city: Aventura
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: N. Miami Beach
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Columbus,
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Chicago Heights
country: United States
state: Illinois
city: Evansville,
country: United States
state: Indiana
city: Des Moines
country: United States
state: Iowa
city: Lafayette
country: United States
state: Louisiana
city: Fall River
country: United States
state: Massachusetts
city: Waltham
country: United States
state: Massachusetts
city: Tupelo
country: United States
state: Mississippi
city: Chesterfield
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Staten Island
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Centerville
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Medford
country: United States
state: Oregon
city: Meadville
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Chattanooga
country: United States
state: Tennessee
city: Morristown
country: United States
state: Tennessee
city: Murfreesboro
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Midland
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Orange
country: United States
state: Virginia
city: Virginia Beach,
country: United States
state: Virginia
city: Man
country: United States
state: West Virginia
city: Wausau
country: United States
state: Wisconsin
city: Carolina
country: Puerto Rico
city: PoncE
country: Puerto Rico
Study officials:
affiliation: Takeda
name: VP Clinical Science Strategy
role: STUDY_DIRECTOR
References:
citation: Berhanu P, Kipnes MS, Khan MA, Perez AT, Kupfer SF, Spanheimer RC, Demissie S, Fleck PR. Effects of pioglitazone on lipid and lipoprotein profiles in patients with type 2 diabetes and dyslipidaemia after treatment conversion from rosiglitazone while continuing stable statin therapy. Diab Vasc Dis Res. 2006 May;3(1):39-44. doi: 10.3132/dvdr.2006.005.