Efficacy and Safety of Azilsartan Medoxomil Used in Combination With Metformin in Participants With Hypertension and Diabetes

NCT ID: NCT01496430

Last Updated: 2015-05-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2013-05-31

Brief Summary

The purpose of this study was to evaluate the antihypertensive and antiglycemic effects, as well as the safety and tolerability of TAK-491 (azilsartan medoxomil), once daily (QD), in stage 1 hypertensive, type 2 diabetes mellitus (T2DM) participants whose glycemic control was inadequate on metformin alone.

Detailed Description

The study included a Screening Period of up to 4 weeks, which coincided with a 2-week single-blind, placebo Run-in Period, a 24 week Treatment Period, and a 2-week Follow-up Period. The duration of the study was approximately 30 weeks. The planned number of participants (n=450) was not reached; actual enrollment consisted of 105 particpants. Due to low enrollment this study was terminated early by Takeda.

Conditions

Hypertension; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo QD

Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Azilsartan Medoxomil 40 mg QD

Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan Medoxomil 80 mg QD

Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Interventions

Placebo

Intervention Type: DRUG

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil

Intervention Type: DRUG

Other Intervention Names

TAK-491; TAK-491

Eligibility Criteria

Inclusion Criteria

1. Was male or female and ≥18 years.

2. Had type 2 diabetes mellitus with HbA1c of ≥7.5 to ≤9.5% at Screening.

3. Was treated with metformin alone (no treatment with any antidiabetic agents other than metformin within the 3 months prior to Screening) and was experiencing inadequate glycemic control. The participant should have received metformin monotherapy for ≥8 weeks prior to Screening at a stable dose ≥1500 mg). Participants with a maximum tolerated dose (MTD) that was documented to be less than 1500 mg of metformin could also be enrolled if this dose had been stable for 8 weeks prior to Screening.

4. Was treated with antihypertensive therapy and had a mean, trough, sitting clinic systolic blood pressure (SBP) ≥135 and < 160 mm Hg on Day -1 (after washout of prior antihypertensive therapy) or the participant had not received antihypertensive treatment within 28 days before Screening and had a mean sitting clinic SBP ≥135 and < 160 mm Hg at the Screening Visit and on Day -1.

5. Had clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or results that were deemed not clinically significant in this participant population for inclusion in this study, by the investigator.

Exclusion Criteria

1. Had a mean, trough, sitting clinic diastolic blood pressure (DBP) ≥ 100 mm Hg at Day -1.

2. Had type 1 or poorly controlled type 2 diabetes mellitus (HbA1c >9.5%) at Screening.

3. Was taking or expected to take an excluded medication.

4. Had a history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.

5. Had clinically significant cardiac conduction defects (for example, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation).

6. Had hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.

7. Had secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome).

8. Had renal dysfunction defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at Screening.

9. Had albuminuria defined as >200 mg/g at Screening.

10. Had known or suspected unilateral or bilateral renal artery stenosis.

11. Had unexplained microhematuria ≥3 RBCs/HPF or macrohematuria at Screening and confirmed on repeat testing.

12. Treatment with antidiabetic agents (sulfonylureas, glucagon-like peptide-1 (GLP-1) analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, thiazolidinediones (TZDs), and/or insulin) other than metformin during the 3 months prior to Screening.

13. Had hyperkalemia as defined by central laboratory normal reference range at Screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Director, Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Green Valley, Arizona, United States

Tempe, Arizona, United States

Tucson, Arizona, United States

Buena Park, California, United States

Hawaiian Gardens, California, United States

Norwalk, California, United States

Paramount, California, United States

Rancho Cucamonga, California, United States

Sacramento, California, United States

San Diego, California, United States

Tustin, California, United States

Denver, Colorado, United States

Bradenton, Florida, United States

Brooksville, Florida, United States

Hallandale, Florida, United States

Jupiter, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Pembroke Pines, Florida, United States

St. Petersburg, Florida, United States

Tampa, Florida, United States

Winter Park, Florida, United States

Roswell, Georgia, United States

Chicago, Illinois, United States

Evergreen Park, Illinois, United States

Gurnee, Illinois, United States

Avon, Indiana, United States

Greenfield, Indiana, United States

Lexington, Kentucky, United States

Paducah, Kentucky, United States

Baltimore, Maryland, United States

Columbia, Missouri, United States

Omaha, Nebraska, United States

Las Vegas, Nevada, United States

Margate City, New Jersey, United States

Albuquerque, New Mexico, United States

Brooklyn, New York, United States

Calabash, North Carolina, United States

Greensboro, North Carolina, United States

Lenoir, North Carolina, United States

Morehead City, North Carolina, United States

Salisbury, North Carolina, United States

Wilmington, North Carolina, United States

Winston-Salem, North Carolina, United States

Centerville, Ohio, United States

Cincinnati, Ohio, United States

Oklahoma City, Oklahoma, United States

Downingtown, Pennsylvania, United States

Fleetwood, Pennsylvania, United States

Reading, Pennsylvania, United States

Providence, Rhode Island, United States

Anderson, South Carolina, United States

Chattanooga, Tennessee, United States

Kingsport, Tennessee, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

North Richland Hills, Texas, United States

Pearland, Texas, United States

San Antonio, Texas, United States

Salt Lake City, Utah, United States

Burke, Virginia, United States

Manassas, Virginia, United States

Richmond, Virginia, United States

Virginia Beach, Virginia, United States

Wauwatosa, Wisconsin, United States

Countries

United States

Other Identifiers

U1111-1125-1197

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-491_304

Identifier Type: -

Identifier Source: org_study_id