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”

The purpose of this study is to measure the triglyceride changes in subjects with type 2 diabetes mellitus taking pioglitazone following treatment conversion from rosiglitazone.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Study Primary Completion Date: August 2004

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.

Intervention(s) in this Clinical Trial

• Drug: Pioglitazone and statin therapy
  • Pioglitazone 30 mg to 45 mg, tablets, orally, once daily in combination with stable statin therapy for up to 17 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1.

Primary Measures

• Change from Baseline in Triglyceride Levels
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No

Secondary Measures

• Change from Baseline in Total Cholesterol
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in direct Low Density Lipoprotein cholesterol
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in High Density Lipoprotein cholesterol
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in apolipoprotein B (apoB)
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in apolipoprotein A1 (apoA1)
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in Free Fatty Acids
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in Lipid Fractionation
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No
• Change from Baseline in C-reactive Protein
  • Time Frame: Weeks 8 and 17 or Final Visit
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

VP Clinical Science Strategy Study Director Takeda Global Research & Development Center, Inc.  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00672919

Study ID Number: 01-03-TL-OPI-523

ClinicalTrials.gov Identifier: NCT00672919

Health Authority: United States: Food and Drug Administration

ACTOS® Package Insert

FDA Safety Alerts and Recalls