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

June 17, 2010 updated by: Takeda

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

96

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
      • Cordoba, Argentina
      • Santa Fe, Argentina
  • Chile
      • Santiago, Chile
      • Temuco, Chile
  • Mexico
      • Guadalajara, Mexico
      • Mexico, DF, Mexico
    • Guanajuato
      • Leon, Guanajuato, Mexico
    • Jalisco
      • Zapopan, Jalisco, Mexico
    • NL
      • Monterrey, NL, Mexico
  • Peru
      • Arequipa, Peru
      • Lambayeque, Peru
      • Lima, Peru
      • Trujillo, Peru
  • United States
    • Alabama
      • Huntsville, Alabama, United States
      • Tallassee, Alabama, United States
    • Arkansas
      • Little Rock, Arkansas, 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
    • 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
    • Georgia
      • Augusta, Georgia, United States
      • Dunwoody, Georgia, United States
    • Illinois
      • Chicago, Illinois, United States
    • Indiana
      • Bloomington, Indiana, United States
      • Evansville, Indiana, United States
    • Kansas
      • Shawnee Mission, Kansas, United States
    • Maryland
      • Prince Frederick, Maryland, United States
    • Michigan
      • Livonia, Michigan, United States
      • St. Clair Shores, Michigan, United States
    • Nevada
      • Las Vegas, Nevada, United States
    • New Jersey
      • Trenton, New Jersey, United States
    • New York
      • Albany, New York, United States
      • Johnson City, New York, United States
      • Staten Island, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
      • Salisbury, North Carolina, United States
      • Winston-Salem, North Carolina, United States
    • Ohio
      • Marion, Ohio, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Pennsylvania
      • Buckingham, Pennsylvania, United States
      • Jeannette, Pennsylvania, United States
    • South Carolina
      • Mt. Pleasant, South Carolina, United States
      • Simpsonville, South Carolina, United States
    • Tennessee
      • Bristol, Tennessee, United States
      • New Tazewell, Tennessee, 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
    • Virginia
      • Falls Church, Virginia, United States
      • Virginia Beach, Virginia, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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
EXPERIMENTAL: Pioglitazone 45 mg/Azilsartan 40 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Glycosylated Hemoglobin.
Time Frame: Baseline and Week 24
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.
Baseline and Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Diastolic Blood Pressure
Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24.
The change between Diastolic Blood Pressure measured at each week indicated including final visit and Diastolic Blood Pressure measured at baseline.
Baseline and Weeks 4, 8, 12, 16, 20, and 24.
Change from Baseline in Systolic Blood Pressure
Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
The change between Systolic Blood Pressure measured at each week indicated including final visit and Systolic Blood Pressure measured at baseline.
Baseline and Weeks 4, 8, 12, 16, 20, and 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Takeda

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (ACTUAL)

May 1, 2007

Study Completion (ACTUAL)

May 1, 2007

Study Registration Dates

First Submitted

September 12, 2006

First Submitted That Met QC Criteria

September 12, 2006

First Posted (ESTIMATE)

September 14, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

June 22, 2010

Last Update Submitted That Met QC Criteria

June 17, 2010

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-06-TL-OPI536-003
  • U1111-1114-1098 (REGISTRY: WHO)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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