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

This study has been terminated.
(Formulation issues.)
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01124656
First received: May 13, 2010
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
Diabetes Mellitus, Type 2
Drug: Pioglitazone-Azilsartan
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

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


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


Enrollment: 26
Study Start Date: September 2006
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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.
  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: NCT01124656

Sponsors and Collaborators
Takeda
Investigators
Study Director: VP, Clinical Science Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01124656     History of Changes
Other Study ID Numbers: 01-06-TL-OPI536-005, U1111-1114-6658
Study First Received: May 13, 2010
Last Updated: May 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
angiotensin II receptor blocker
thiazolidinediones
combination
Actos
HbA1c
Type 2 diabetes
Drug Therapy
Hypertension

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 October 22, 2014