Back to resultsSafety and Tolerability of Pioglitazone-Azilsartan in Subjects With Type 2 Diabetes
Primary Purpose
Diabetes Mellitus, Type 2
Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pioglitazone-Azilsartan
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring angiotensin II receptor blocker, thiazolidinediones, combination, Actos, HbA1c, Type 2 diabetes, Drug Therapy, Hypertension
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pioglitazone-Azilsartan QD
Arm Description
(Dependent on glycosylated hemoglobin level at screening)
Outcomes
Primary Outcome Measures
Incidence of Adverse Events.
The Incidence of Treatment-Emergent Adverse Events, with an incidence > 5%.
Secondary Outcome Measures
Change from Baseline for Glycosylated Hemoglobin.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01124656
Brief Title
Safety and Tolerability of Pioglitazone-Azilsartan in Subjects With Type 2 Diabetes
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 Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Terminated
Why Stopped
Formulation issues.
Study Start Date
September 2006 (undefined)
Primary Completion Date
May 2007 (Actual)
Study Completion Date
May 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
angiotensin II receptor blocker, thiazolidinediones, combination, Actos, HbA1c, Type 2 diabetes, Drug Therapy, Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone-Azilsartan QD
Arm Type
Experimental
Arm Description
(Dependent on glycosylated hemoglobin level at screening)
Intervention Type
Drug
Intervention Name(s)
Pioglitazone-Azilsartan
Other Intervention Name(s)
Pioglitazone, Actos, Azilsartan, AD-4833, TAK-536
Intervention Description
Pioglitazone-Azilsartan (30 mg + 20 mg) or (45 mg + 20 mg), tablets, orally, once daily for up to 52 weeks.
Primary Outcome Measure Information:
Title
Incidence of Adverse Events.
Description
The Incidence of Treatment-Emergent Adverse Events, with an incidence > 5%.
Time Frame
On Occurrence (up to 52 Weeks).
Secondary Outcome Measure Information:
Title
Change from Baseline for Glycosylated Hemoglobin.
Description
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.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48 and 52.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
VP, Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Safety and Tolerability of Pioglitazone-Azilsartan in Subjects With Type 2 Diabetes
We'll reach out to this number within 24 hrs