Efficacy and Safety of Pioglitazone and Azilsartan in Treating Subjects With Type 2 Diabetes Mellitus

NCT ID: NCT00762736

Last Updated: 2012-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 704 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2005-10-31

Brief Summary

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.

Detailed Description

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.

Conditions

Diabetes Mellitus

Study Design

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

Study Groups

Pioglitazone 15 mg QD + Azilsartan 5 mg QD

Group Type: EXPERIMENTAL

Pioglitazone and azilsartan

Intervention Type: DRUG

Pioglitazone 15 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.

Pioglitazone 15 mg QD + Azilsartan 40 mg QD

Group Type: EXPERIMENTAL

Pioglitazone and azilsartan

Intervention Type: DRUG

Pioglitazone 15 mg, tablets, orally, once daily and azilsartan 40 mg, tablets, orally, once daily for up to 24 weeks.

Pioglitazone 15 mg QD

Group Type: ACTIVE_COMPARATOR

Pioglitazone

Intervention Type: DRUG

Pioglitazone 15 mg, tablets, orally, once daily and azilsartan placebo-matching tablets, orally, once daily for up to 24 weeks.

Pioglitazone 45 mg QD + Azilsartan 5 mg QD

Group Type: EXPERIMENTAL

Pioglitazone and azilsartan

Intervention Type: DRUG

Pioglitazone 45 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.

Pioglitazone 45 mg QD + Azilsartan 40 mg QD

Group Type: EXPERIMENTAL

Pioglitazone and azilsartan

Intervention Type: DRUG

Pioglitazone 45 mg, tablets, orally, once daily and azilsartan 40 mg, tablets, orally, once daily for up to 24 weeks.

Pioglitazone 45 mg QD

Group Type: ACTIVE_COMPARATOR

Pioglitazone

Intervention Type: DRUG

Pioglitazone 45 mg, tablets, orally, once daily and azilsartan placebo-matching tablets, orally, once daily for up to 24 weeks.

Interventions

Pioglitazone and azilsartan

Pioglitazone 15 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Pioglitazone and azilsartan

Pioglitazone 15 mg, tablets, orally, once daily and azilsartan 40 mg, tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Pioglitazone

Pioglitazone 15 mg, tablets, orally, once daily and azilsartan placebo-matching tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Pioglitazone and azilsartan

Pioglitazone 45 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Pioglitazone and azilsartan

Pioglitazone 45 mg, tablets, orally, once daily and azilsartan 40 mg, tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Pioglitazone

Pioglitazone 45 mg, tablets, orally, once daily and azilsartan placebo-matching tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

ACTOS®; AD4833; TAK-536; ACTOS®; AD4833; TAK-536; ACTOS®; AD4833; ACTOS®; AD4833; TAK-536; ACTOS®; AD4833; TAK-536; ACTOS®; AD4833

Eligibility Criteria

Inclusion Criteria

• Had type 2 diabetes, with a hemoglobin value of greater than or equal to 8.0% or less than 10.0% at Screening.
• Females of childbearing potential who were sexually active agreed to use adequate contraception, and were neither pregnant nor lactating from Screening throughout the duration of the study.
• Received antihypertensive therapy and must have been on a stable dose for a minimum of 8 weeks prior to Screening.
• Had clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory unless the results were deemed not clinically significant for inclusion into this study by the investigator or sponsor.
• Had been on stable diet and exercise program and oral anti-glycemic therapy including sulfonylurea or metformin for 8 weeks prior to Screening.

Exclusion Criteria

• Had a hemoglobin value less than 8.0% or greater than 10.0% at Screening.
• Was taking an angiotensin II receptor blocker.
• Had uncontrolled hypertension defined as systolic blood pressure greater than 160 mm Hg and diastolic blood pressure greater than 100 mm Hg. - Had a systolic blood pressure less than or equal to 110 mm Hg and/or diastolic blood pressure less than or equal to 60 mm Hg.
• Was taking or was expected to take the following medications:

• antidiabetic agents (other than sulfonylurea or metformin)
• tricyclic antidepressants
• monoamine oxidase inhibitors
• phenothiazines
• diet medications
• amphetamines or their derivatives
• lithium
• common cold medications with chronic use
• nonsteroidal anti-inflammatory drugs with chronic use (including aspirin greater than 325 mg/day or cyclooxygenase 2 inhibitors).
• Had unstable angina or heart failure of any etiology with functional class New York Heart Association III or IV.
• Had a history of myocardial infarction.
• Had clinically significant cardiac conduction defects (eg, second or third degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).
• Had secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
• Had a history of collagen vascular disorder (eg, systemic lupus erythematosus, scleroderma) within the last 5 years.
• Had a body mass index greater than 39 kg/m2.
• Had significant, moderate-to-severe renal dysfunction (creatinine greater than 2.4 mg/dL). If receiving metformin, a creatinine greater than 1.5 mg/dL for male subjects or greater than 1.4 mg/dL for female subjects led to exclusion.
• Had a history of drug abuse or a history of alcohol abuse within the past 2 years.
• Had a previous history of cancer, other than basal cell carcinoma, that had not been in remission for at least 5 years prior to the first dose of study drug.
• Had type 2 diabetes with clinically important retinopathy or peripheral or autonomic neuropathy.
• Had an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
• Was participating in another investigational study or had participated in an investigational study within 30 days prior to randomization.
• Had any other serious disease or condition at Screening (or randomization) that might have compromised subject safety, affected life expectancy, or made it difficult to successfully manage and follow the subject according to the protocol.
• Was hypersensitive to angiotensin II receptor blockers.
• Was hypersensitive to thiazolidinediones.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VP Clinical Science Strategy

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Sierra Vista, Arizona, United States

Sun City, Arizona, United States

Tucson, Arizona, United States

Burbank, California, United States

Escondido, California, United States

Irvine, California, United States

La Jolla, California, United States

National City, California, United States

Riverside, California, United States

Sacramento, California, United States

San Diego, California, United States

Spring Valley, California, United States

Coral Gables, Florida, United States

DeLand, Florida, United States

Hollywood, Florida, United States

Miami, Florida, United States

New Port Richey, Florida, United States

Opa-locka, Florida, United States

Pembroke Pines, Florida, United States

Sarasota, Florida, United States

Vero Beach, Florida, United States

Atlanta, Georgia, United States

Augusta, Georgia, United States

Warner Robins, Georgia, United States

Honolulu, Hawaii, United States

Lihue, Hawaii, United States

Chicago, Illinois, United States

Dyersburg, Indiana, United States

Overland Park, Kansas, United States

Wichita, Kansas, United States

New Orleans, Louisiana, United States

Shreveport, Louisiana, United States

Salisbury, Massachusetts, United States

Cadillac, Michigan, United States

Detroit, Michigan, United States

Livonia, Michigan, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

Las Vegas, Nevada, United States

North Las Vegas, Nevada, United States

Berlin, New Jersey, United States

Blackwood, New Jersey, United States

Trenton, New Jersey, United States

Albany, New York, United States

Kingston, New York, United States

Charlotte, North Carolina, United States

Marion, Ohio, United States

Clinton, Oklahoma, United States

Oklahoma City, Oklahoma, United States

Allentown, Pennsylvania, United States

Altoona, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Scotland, Pennsylvania, United States

Woonsocket, Rhode Island, United States

Greer, South Carolina, United States

Arlington, Texas, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Midland, Texas, United States

North Richard Hills, Texas, United States

San Antonio, Texas, United States

Renton, Washington, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Rosario-Santa Fe, , Argentina

Santa Fe, , Argentina

Ushuaia - Tierre Del Fuego, , Argentina

Santiago, , Chile

Aguascalientes, , Mexico

Cuernavaca, , Mexico

Durango, , Mexico

Guadalajara, , Mexico

Mexico City, , Mexico

Puebla City, , Mexico

Ica, , Peru

Lima, , Peru

Countries

United States; Argentina; Chile; Mexico; Peru

Related Links

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

Actos Package Insert

Other Identifiers

U1111-1115-8992

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-04-TL-OPI-525

Identifier Type: -

Identifier Source: org_study_id