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

May 18, 2012 updated by: Takeda

A One-Year Phase 3, Open-Label Study to Evaluate the Safety and Tolerability of AD 4833-536 in Subjects With Type 2 Diabetes

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Enrollment (Actual)

26

Phase

  • Phase 3

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:

  • 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.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Actos
  • AD-4833
  • Pioglitazone
  • TAK-536
  • Azilsartan

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48 and 52.

Collaborators and Investigators

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

Sponsor

Takeda

Investigators

  • Study Director: VP, Clinical Science, 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

September 1, 2006

Primary Completion (Actual)

May 1, 2007

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

May 13, 2010

First Submitted That Met QC Criteria

May 13, 2010

First Posted (Estimate)

May 17, 2010

Study Record Updates

Last Update Posted (Estimate)

May 21, 2012

Last Update Submitted That Met QC Criteria

May 18, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-06-TL-OPI536-005
  • U1111-1114-6658 (Registry Identifier: 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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