Azilsartan Medoxomil (TAK-491) Compared to Placebo in Korean Adults With Hypertension

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-491 in Korean Subjects With Essential Hypertension

The purpose of this study is to compare the antihypertensive effect of azilsartan medoxomil versus placebo in Korean adults with essential hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Azilsartan medoxomil; Drug: Azilsartan medoxomil placebo

Detailed Description

The drug being tested in this study is called azilsartan medoxomil. Azilsartan medoxomil is being tested to treat Korean adults with hypertension. This study will look at changes in blood pressure in people who take azilsartan medoxomil.

The study will enroll approximately 325 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Azilsartan medoxomil 40 mg
• Azilsartan medoxomil 80 mg
• Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.

All participants will be asked to take two tablets at the same time each day throughout the study.

This multi-centre trial will be conducted in Korea. The overall time to participate in this study is 12 weeks. Participants will make 7 visits to the clinic, and will be contacted by telephone 7 days after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 328
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
  • Daegu, Korea, Republic of
  • Daejeon, Korea, Republic of
  • Incheon, Korea, Republic of
  • Seoul, Korea, Republic of
  • Gangwon-do
    • Chuncheon-Si, Gangwon-do, Korea, Republic of
    • Wonju-Si, Gangwon-do, Korea, Republic of
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, Korea, Republic of
    • Goyang-si, Gyeonggi-do, Korea, Republic of
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
    • Suwon-si, Gyeonggi-do, Korea, Republic of
  • Gyeongsangbuk-do
    • Daegu, Gyeongsangbuk-do, Korea, Republic of
  • Gyeongsangnam-do
    • Yangsan-si, Gyeongsangnam-do, Korea, Republic of
  • Jeollabuk-do
    • Jeonju-si, Jeollabuk-do, Korea, Republic of
  • Jeollanam-do
    • Gwangju, Jeollanam-do, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative, signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure (SBP) ≥150 and ≤180 mm Hg on Day 1; or the patient has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic SBP ≥150 and ≤180 mm Hg at the Screening Visit and on Day 1.
4. Is male or female aged ≥19 years.
5. A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent through 30 days after last study drug dose.
6. Is willing to discontinue current antihypertensive medications on Day -21. If on amlodipine or chlorthalidone prior to Screening, the participant is willing to discontinue this medication on Day -28.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to the first dose of study medication.
2. Has received TAK-491 in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4. Has sitting trough clinic diastolic blood pressure (DBP) greater than 114 mm Hg at Day 1 (after placebo run-in).
5. Has a history of hypersensitivity to TAK-491 (azilsartan medoxomil), any of its excipients, or other angiotensin-converting enzyme (ARBs).
6. Has a history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
7. Has clinically significant cardiac conduction defects (e.g., 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation, or flutter).
8. Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease and hypertrophic obstructive cardiomyopathy (HOCM).
9. Has secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing syndrome).
10. Is noncompliant (less than 70% or greater than 130%) with study medication during placebo run-in period.
11. Has severe renal dysfunction or disease (confirmed by calculated creatinine clearance <30 mL/min/1.73m^2) at Screening.
12. Has known or suspected unilateral or bilateral renal artery stenosis.
13. Has a history of drug or alcohol abuse within the past 2 years.
14. Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not apply to those patients with basal cell or stage I squamous cell carcinoma of the skin.)
15. Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c]>8.0%) at Screening.
16. Has an alanine aminotransferase (ALT) level greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
17. Has hyperkalemia (defined as serum potassium greater than the upper limit of normal per the central laboratory) at Screening.
18. Has any other serious disease or condition at screening or randomization that would compromise participant safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.
19. Is required to take excluded medications.
20. If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Azilsartan Medoxomil 40 mg; Azilsartan medoxomil 40 mg, tablets, orally, once daily for 6 weeks.	Drug: Azilsartan medoxomil; Azilsartan medoxomil tablets; Other Names: TAK-491
EXPERIMENTAL: Azilsartan Medoxomil 80 mg; Azilsartan medoxomil 80 mg, tablets, orally, once daily for 6 weeks.	Drug: Azilsartan medoxomil; Azilsartan medoxomil tablets; Other Names: TAK-491
PLACEBO_COMPARATOR: Placebo; Azilsartan medoxomil placebo-matching tablets, orally, once daily for 6 weeks.	Drug: Azilsartan medoxomil placebo; Azilsartan medoxomil placebo-matching tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in Trough Clinic Sitting Systolic Blood Pressure (SBP)	The change in trough clinic sitting systolic blood pressure measured at week 6 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting systolic blood pressure measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 blood pressure was measured approximately 24 hours after the previous day's dose. An analysis of covariance (ANCOVA) model, with treatment group as a fixed effect and Baseline sitting clinic systolic blood pressure as a covariate was used for analysis.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in Trough Clinic Sitting Diastolic Blood Pressure (DBP)	The change in trough clinic sitting diastolic blood pressure measured at week 6 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting diastolic blood pressure measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 blood pressure was measured approximately 24 hours after the previous day's dose. An analysis of covariance (ANCOVA) model, with treatment group as a fixed effect and Baseline sitting clinic diastolic blood pressure as a covariate was used for analysis.	Baseline and Week 6
Percentage of Participants Who Achieved a Clinic DBP Response at Week 6	Clinic DBP response is defined as clinic DBP <90 mmHg and/or reduction of ≥10 mmHg from Baseline. DBP is the arithmetic mean of 3 serial diastolic blood pressure measurements.	Baseline and Week 6
Percentage of Participants Who Achieved a Clinic SBP Response at Week 6	SBP response is defined as clinic SBP <140 mmHg and/or reduction of ≥20 mmHg from Baseline. SBP is the arithmetic mean of 3 serial systolic blood pressure measurements.	Baseline and Week 6
Percentage of Participants Who Achieved Both a Clinic DBP and SBP Response at Week 6	Percentage of participants who achieved both a clinic DBP and SBP response measured at week 6 defined as clinic DBP <90 mmHg and/or reduction of ≥10 mmHg from Baseline AND clinic SBP <140 mmHg and/or reduction of ≥20 mmHg from Baseline. DBP and SBP are based on the arithmetic mean of 3 serial blood pressure measurements.	Baseline and Week 6

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Juhasz A, Wu J, Hisada M, Tsukada T, Jeong MH. Efficacy and safety of azilsartan medoxomil, an angiotensin receptor blocker, in Korean patients with essential hypertension. Clin Hypertens. 2018 Feb 7;24:2. doi: 10.1186/s40885-018-0086-4. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: July 28, 2014
• First Posted (ESTIMATE): July 30, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Azilsartan medoxomil
• Other Study ID Numbers: TAK-491_307; U1111-1130-9186 (OTHER: WHO)