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Efficacy, Safety and Tolerability of Pioglitazone-Azilsartan in Subjects With Type 2 Diabetes Mellitus

This study has been terminated.
(Combination formulation concerns)
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00376181
First received: September 12, 2006
Last updated: June 17, 2010
Last verified: June 2010
  Purpose

The purpose of this study is to evaluate the efficacy and safety of pioglitazone-azilsartan, once daily (QD), in subjects with type 2 diabetes mellitus with poor glycemic control.


Condition Intervention Phase
Type 2 Diabetes
Drug: Pioglitazone and Azilsartan
Drug: Pioglitazone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Double-Blind, Randomized, Placebo-Controlled Study to Determine the Efficacy, Safety, and Tolerability of AD-4833-536 in the Treatment of Subjects With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 or including final visit, and Glycosylated Hemoglobin collected at baseline.


Secondary Outcome Measures:
  • Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24. ] [ Designated as safety issue: No ]
    The change between Diastolic Blood Pressure measured at each week indicated including final visit and Diastolic Blood Pressure measured at baseline.

  • Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The change between Systolic Blood Pressure measured at each week indicated including final visit and Systolic Blood Pressure measured at baseline.


Enrollment: 96
Study Start Date: June 2006
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone 45 mg/Azilsartan 20 mg QD Drug: Pioglitazone and Azilsartan
Pioglitazone 45 mg and Azilsartan 20 mg combination tablets, orally, once daily for up to 24 weeks.
Other Names:
  • Actos
  • AD-4833
  • TAK-536
Experimental: Pioglitazone 45 mg/Azilsartan 40 mg QD Drug: Pioglitazone and Azilsartan
Pioglitazone 45 mg and Azilsartan 40 mg combination tablets, orally, once daily for up to 24 weeks.
Other Names:
  • Actos
  • AD-4833
  • TAK-536
Active Comparator: Pioglitazone 45 mg QD Drug: Pioglitazone
Pioglitazone 45 mg, tablets, orally, once daily for up to 24 weeks.
Other Names:
  • Actos
  • AD-4833

Detailed Description:

Type 2 diabetes is a chronic disease. In the United States, an estimated 21 million people have diabetes, with type 2 diabetes occurring in 90% to 95% of cases. Hypertension (high blood pressure) affects approximately 50 million individuals in the United States. The association of diabetes and hypertension is increased in this population; hypertension is more common in persons with diabetes while individuals with hypertension are 2.5 times more likely to develop diabetes than those who have normal blood pressure. As a result, more than 70% of adults with diabetes have hypertension (defined as having blood pressure greater than or equal to 130/80 mm Hg or using prescription medication for hypertension).

Patients with type 2 diabetes and hypertension are at high risk of other illnesses and death. Diabetes and hypertension are associated with insulin resistance (normal amounts of insulin are no adequate to produce a normal insulin response from fat, muscle and liver cells). and hyperinsulinemia (excess levels of insulin in the blood), which are independent risk factors for cardiovascular (heart vessel) disease. Individuals with type 2 diabetes carry a 2 to 4- time greater risk of cardiovascular disease and stroke compared with the general population. Uncontrolled hypertension also is associated with an increased risk of cardiovascular disease and stroke.

Takeda Global Research and Development Center, Inc. is developing a fixed-dose combination product, AD-4833-536. AD-4833-536 is a combination of AD-4833 (pioglitazone) and TAK-536 (azilsartan). Pioglitazone is an oral antidiabetic agent that acts by reducing insulin resistance and approved for treatment of adult patients with type 2 diabetes mellitus. Azilsartan is a angiotensin II receptor blocker that modulates the renin-angiotensin-aldosterone system that regulates blood pressure.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Type 2 diabetes with glycosylated hemoglobin of greater than or equal to 9.0 to less than or equal to 11.0% at Screening.
  • Documented hypertension.
  • On a stable diet and exercise program in addition to metformin alone or combination of metformin and a sulfonylurea for a minimum of 8 weeks prior to screening.
  • If receiving antihypertensive therapy, must be on no more than 3 agents and be on a stable regimen.
  • Clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis) within the reference range unless the results are deemed not clinically significant for inclusion into this study by the investigator.
  • 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.

Exclusion Criteria

  • Type 1 diabetes mellitus.
  • Diastolic blood pressure greater than 104 mm Hg at randomization visit.
  • Currently taking an angiotensin II-receptor blocker.
  • Unstable angina or heart failure of any etiology with New York Heart Association functional class III or IV.
  • History of myocardial infarction, cerebrovascular accident (stroke), percutaneous coronary intervention, coronary artery bypass graft or transient ischemic attack within the previous six months.
  • Clinically significant cardiac conduction defects.
  • Secondary hypertension of any etiology.
  • Body mass index greater than 45 kg/m2
  • Has significant renal dysfunction.
  • History of drug abuse or a history of alcohol abuse within the past 2 years.
  • Previous history of cancer, other than basal cell carcinoma or stage 1 squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to the first dose of study drug.
  • Alanine transaminase or aspartate transaminase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
  • Serum potassium greater than the upper limit of normal.
  • Currently participating in another investigational study or has participated in an investigational study within 30 days prior to Randomization.
  • Any other serious disease or condition that would compromise subject safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
  • Is hypersensitive to angiotensin II receptor blockers.
  • Is hypersensitive to thiazolidinediones.
  • Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • any anti-diabetic agent (including thiazolidinediones and/or insulin) except for metformin or a combination of metformin and a sulfonylurea
    • niacin more than 200mg per day
    • tricyclic antidepressants or phenothiazines
    • Angiotensin II receptor blockers
    • Thiazolidinediones
    • Insulin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376181

  Hide Study Locations
Locations
United States, Alabama
Huntsville, Alabama, United States
Tallassee, Alabama, United States
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Auburn, California, United States
Bakersfield, California, United States
Buena Park, California, United States
Chula Vista, California, United States
Huntington Park, California, United States
Los Gatos, California, United States
Norwalk, California, United States
Orangevale, California, United States
Sacramento, California, United States
Stockton, California, United States
United States, Florida
Deerfield Beach, Florida, United States
Hialeah, Florida, United States
Hollywood, Florida, United States
Jacksonville, Florida, United States
Kissimmee, Florida, United States
Marianna, Florida, United States
Melbourne, Florida, United States
Miami, Florida, United States
Pembroke Pines, Florida, United States
Winter Haven, Florida, United States
United States, Georgia
Augusta, Georgia, United States
Dunwoody, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Bloomington, Indiana, United States
Evansville, Indiana, United States
United States, Kansas
Shawnee Mission, Kansas, United States
United States, Maryland
Prince Frederick, Maryland, United States
United States, Michigan
Livonia, Michigan, United States
St. Clair Shores, Michigan, United States
United States, Nevada
Las Vegas, Nevada, United States
United States, New Jersey
Trenton, New Jersey, United States
United States, New York
Albany, New York, United States
Johnson City, New York, United States
Staten Island, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
Salisbury, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Ohio
Marion, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Buckingham, Pennsylvania, United States
Jeannette, Pennsylvania, United States
United States, South Carolina
Mt. Pleasant, South Carolina, United States
Simpsonville, South Carolina, United States
United States, Tennessee
Bristol, Tennessee, United States
New Tazewell, Tennessee, United States
United States, Texas
Dallas, Texas, United States
El Paso, Texas, United States
Euless, Texas, United States
Fort Worth, Texas, United States
Houston, Texas, United States
McKinney, Texas, United States
Midland, Texas, United States
North Richland Hills, Texas, United States
San Antonio, Texas, United States
United States, Virginia
Falls Church, Virginia, United States
Virginia Beach, Virginia, United States
Argentina
Buenos Aires, Argentina
Cordoba, Argentina
Santa Fe, Argentina
Chile
Santiago, Chile
Temuco, Chile
Mexico
Leon, Guanajuato, Mexico
Zapopan, Jalisco, Mexico
Monterrey, NL, Mexico
Guadalajara, Mexico
Mexico, DF, Mexico
Peru
Arequipa, Peru
Lambayeque, Peru
Lima, Peru
Trujillo, Peru
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Clinical Science Strategy Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00376181     History of Changes
Other Study ID Numbers: 01-06-TL-OPI536-003, U1111-1114-1098
Study First Received: September 12, 2006
Last Updated: June 17, 2010
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Chile: Instituto de Salud Pública de Chile
Mexico: Ministry of Health

Keywords provided by Takeda:
type 2 diabetes
hypertension
blood pressure
diastolic blood pressure

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014