The purpose of this study is to determine the efficacy of pioglitazone, once daily (QD), combined with azilsartan in the treatment of subjects with Type 2 Diabetes Mellitus.
Diabetes 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, body constitution 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 and peripheral-tissue cells to circulating insulin (i.e., insulin resistance) to a progressive inability of the body to produce adequate insulin to overcome insulin resistance (i.e., 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 90-95% of cases. Therapeutic agents have been developed to address each of the major functional metabolic defects associated with type 2 diabetes: decreased beta-cell function, elevated hepatic glucose output, and insulin resistance. The oral therapeutic agents used in the treatment of type 2 diabetes can be separated into the following four categories based on their mechanisms of action: insulin secretagogues, inhibitors of hepatic glucose output, inhibitors of complex carbohydrate breakdown in the intestine and insulin sensitizers. Thiazolidinediones reduce insulin resistance by enhancing insulin sensitivity in muscle cells, adipose tissue, and hepatic cells (inhibiting hepatic gluconeogenesis) with no direct impact on insulin secretion. Thus thiazolidinediones improve glycemic control and result in reduced levels of circulating insulin. Peroxisome proliferator-activated receptors are found in tissues important for insulin action, such as adipose tissue, skeletal muscle, and the liver. The greatest concentration of peroxisome proliferator-activated receptors -gamma receptors is in adipose tissue. Pioglitazone HCl (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. Research suggests that Angiotensin II receptor blockers are involved in endothelial and cardiovascular function, and in insulin sensitization and obesity. TAK-536 (azilsartan) is an angiotensin II receptor antagonist with affinity for and selective antagonistic activity at the angiotensin II type 1 receptor. This study was designed to evaluate the efficacy, safety, and tolerability of pioglitazone in combination with azilsartan in subjects with type 2 diabetes. Study participation is anticipated to be approximately 6 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
704
Pioglitazone 15 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.
Pioglitazone 15 mg, tablets, orally, once daily and azilsartan 40 mg, tablets, orally, once daily for up to 24 weeks.
Pioglitazone 15 mg, tablets, orally, once daily and azilsartan placebo-matching tablets, orally, once daily for up to 24 weeks.
Change from Baseline in glycosylated hemoglobin.
Time frame: Week 24 or Final Visit
Change from Baseline in glycosylated hemoglobin.
Time frame: Weeks 12, 16, 20, and 24 or Final Visit
Change from Baseline in fasting plasma glucose.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in total cholesterol.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in high-density lipoprotein.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in low-density lipoprotein.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in triglycerides.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in body weight.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in systolic and diastolic blood pressure.
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
Change from Baseline in incidence of edema (peripheral).
Time frame: Weeks 2, 4, 6, 8. 12, 16, 20, and 24 or Final Visit
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Pioglitazone 45 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.
Pioglitazone 45 mg, tablets, orally, once daily and azilsartan 40 mg, tablets, orally, once daily for up to 24 weeks.
Pioglitazone 45 mg, tablets, orally, once daily and azilsartan placebo-matching tablets, orally, once daily for up to 24 weeks.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Huntsville, Alabama, United States
Unnamed facility
Sierra Vista, Arizona, United States
Unnamed facility
Sun City, Arizona, United States
Unnamed facility
Tucson, Arizona, United States
Unnamed facility
Burbank, California, United States
Unnamed facility
Escondido, California, United States
Unnamed facility
Irvine, California, United States
Unnamed facility
La Jolla, California, United States
Unnamed facility
National City, California, United States
...and 68 more locations
Change from Baseline in microalbuminuria excretion.
Time frame: Week 24 or Final Visit
Change from Baseline in high-sensitivity C-reactive protein.
Time frame: Weeks 12 and 24 or Final Visit
Change from Baseline in matrix metalloproteinase-9.
Time frame: Weeks 12 and 24 or Final Visit