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

NCT01496430 | Terminated Phase 3 Results

• 2 other identifiers: TAK-491_304U1111-1125-1197
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 68

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.

Conditions

Hypertension; Diabetes

Keywords

Drug Therapy; Hypertension and Diabetes

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure

  The change in trough systolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.

  Baseline and Week 8

Secondary Outcomes (22)

• Change From Baseline in Glycosylated Hemoglobin (HbA1c)

  Baseline and Week 24

• Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure

  Baseline and Week 8

• Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8

• Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8

• Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8

Study Arms (3)

Placebo QD

PLACEBO COMPARATOR

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

Drug: Placebo

Azilsartan Medoxomil 40 mg QD

EXPERIMENTAL

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

Drug: Azilsartan medoxomil

Azilsartan Medoxomil 80 mg QD

EXPERIMENTAL

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

Drug: Azilsartan medoxomil

Interventions

Placebo DRUG

Placebo QD

Azilsartan medoxomil DRUG

Also known as: TAK-491

Azilsartan Medoxomil 40 mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Was male or female and ≥18 years.
• Had type 2 diabetes mellitus with HbA1c of ≥7.5 to ≤9.5% at Screening.
• 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.
• 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.

You may not qualify if:

• Had a mean, trough, sitting clinic diastolic blood pressure (DBP) ≥ 100 mm Hg at Day -1.
• Had type 1 or poorly controlled type 2 diabetes mellitus (HbA1c \>9.5%) at Screening.
• Was taking or expected to take an excluded medication.
• 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.
• Had clinically significant cardiac conduction defects (for example, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation).
• Had hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
• Had secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome).
• Had renal dysfunction defined as estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 at Screening.
• Had albuminuria defined as \>200 mg/g at Screening.
• Had known or suspected unilateral or bilateral renal artery stenosis.
• Had unexplained microhematuria ≥3 RBCs/HPF or macrohematuria at Screening and confirmed on repeat testing.
• 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.
• Had hyperkalemia as defined by central laboratory normal reference range at Screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (68)

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Birmingham, Alabama, United States

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Green Valley, Arizona, United States

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Tempe, Arizona, United States

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Tucson, Arizona, United States

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Buena Park, California, United States

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Hawaiian Gardens, California, United States

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Norwalk, California, United States

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Paramount, California, United States

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Rancho Cucamonga, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Tustin, California, United States

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Denver, Colorado, United States

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Bradenton, Florida, United States

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Brooksville, Florida, United States

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Hallandale, Florida, United States

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Jupiter, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Roswell, Georgia, United States

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Chicago, Illinois, United States

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Evergreen Park, Illinois, United States

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Gurnee, Illinois, United States

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Avon, Indiana, United States

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Greenfield, Indiana, United States

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Lexington, Kentucky, United States

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Paducah, Kentucky, United States

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Baltimore, Maryland, United States

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Columbia, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Margate City, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Calabash, North Carolina, United States

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Greensboro, North Carolina, United States

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Lenoir, North Carolina, United States

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Morehead City, North Carolina, United States

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Salisbury, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Centerville, Ohio, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Downingtown, Pennsylvania, United States

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Fleetwood, Pennsylvania, United States

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Reading, Pennsylvania, United States

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Providence, Rhode Island, United States

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Anderson, South Carolina, United States

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Chattanooga, Tennessee, United States

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Kingsport, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Irving, Texas, United States

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North Richland Hills, Texas, United States

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Pearland, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Burke, Virginia, United States

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Manassas, Virginia, United States

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Richmond, Virginia, United States

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Virginia Beach, Virginia, United States

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Wauwatosa, Wisconsin, United States

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MeSH Terms

Conditions

Hypertension; Diabetes Mellitus

Interventions

azilsartan medoxomil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

Because of low enrollment in the study, the sample sizes in the results data do not allow for significant interpretation of the results.

Results Point of Contact

• Title: Medical Director; Clinical Science
• Organization: Takeda

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Director, Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2011
• First Posted: December 21, 2011
• Study Start: January 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: May 6, 2015
• Results First Posted: May 6, 2015

Record last verified: 2015-04

Locations

US (68)