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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01124656
Recruitment Status : Terminated (Formulation issues.)
First Posted : May 17, 2010
Last Update Posted : May 21, 2012
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to determine the safety and tolerability of pioglitazone-azilsartan, once daily (QD), in patients with type 2 diabetes mellitus.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Pioglitazone-Azilsartan Phase 3

Detailed Description:

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. In a recent clinical trial conducted in subjects with moderately poor to poor control of their type 2 diabetes mellitus, azilsartan coadministered with pioglitazone showed a reduction in hemoglobin A1C and fasting plasma glucose levels.

After a one week screening period, subjects will be stratified to receive a starting dose of pioglitazone-azilsartan (30 mg + 20 mg or 45 mg + 20 mg).

The planned open-label treatment period was 52 weeks; however due to formulation issues, the study was prematurely discontinued and efficacy data were not analyzed.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A One-Year Phase 3, Open-Label Study to Evaluate the Safety and Tolerability of AD 4833-536 in Subjects With Type 2 Diabetes
Study Start Date : September 2006
Actual Primary Completion Date : May 2007
Actual Study Completion Date : May 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pioglitazone-Azilsartan QD
(Dependent on glycosylated hemoglobin level at screening)
Drug: Pioglitazone-Azilsartan
Pioglitazone-Azilsartan (30 mg + 20 mg) or (45 mg + 20 mg), tablets, orally, once daily for up to 52 weeks.
Other Names:
  • Pioglitazone
  • Actos
  • Azilsartan
  • AD-4833
  • TAK-536

Primary Outcome Measures :
  1. Incidence of Adverse Events. [ Time Frame: On Occurrence (up to 52 Weeks). ]
    The Incidence of Treatment-Emergent Adverse Events, with an incidence > 5%.

Secondary Outcome Measures :
  1. Change from Baseline for Glycosylated Hemoglobin. [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48 and 52. ]
    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 each week indicated including final visit, and Glycosylated Hemoglobin collected at baseline.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Has type 2 diabetes with glycosylated hemoglobin ≥7.0 % to ≤ 11.0% at Screening.
  • Has been on a stable diabetic diet/exercise program.
  • If receiving anti-glycemic therapy, he/she must be on ≤ two (2) anti-glycemic agents and be on a stable regimen for a minimum of 8 weeks prior to Screening.
  • Has clinical laboratory evaluations at Screening (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator.
  • A female subject of childbearing potential who is sexually active agrees to use adequate contraception from screening throughout the duration of the study.

Exclusion Criteria:

  • Currently taking or is expected to take thiazolidinediones within 12 weeks of Screening.
  • Hypersensitive to thiazolidinediones.
  • Hypertension with diastolic blood pressure >100 mm Hg and/or systolic blood pressure >170 mm Hg at Screening and/or Visit 2 (Day 1).
  • Currently taking an angiotensin II-receptor blocker (ARB) and is not willing to discontinue therapy at Visit 2 (day 1) and remain off for the duration of the study.
  • Hypersensitive to 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 , percutaneous coronary intervention, coronary artery bypass graft or transient ischemic attack within the previous six months.
  • Clinically significant cardiac conduction defects
  • Body mass index >45 kg/m2 at Screening.
  • Moderate to severe renal dysfunction
  • Anemia
  • Hematuria (>1+ blood) at Screening.
  • Triglycerides >600 mg/dL at Screening.
  • Hyperkalemia, defined as serum potassium level of greater than the upper limit of normal, per the central laboratory at Screening.
  • Alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01124656

Sponsors and Collaborators
Study Director: VP, Clinical Science Takeda

Additional Information:
Responsible Party: Takeda Identifier: NCT01124656     History of Changes
Other Study ID Numbers: 01-06-TL-OPI536-005
U1111-1114-6658 ( Registry Identifier: WHO )
First Posted: May 17, 2010    Key Record Dates
Last Update Posted: May 21, 2012
Last Verified: May 2012

Keywords provided by Takeda:
angiotensin II receptor blocker
Type 2 diabetes
Drug Therapy

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