HypertensionPhase 3NCT02203916

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

A Phase 3 study testing Azilsartan medoxomil in people with Hypertension, run by Takeda at 15 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 19 years and older
Conditions the study is for: Hypertension
What is being tested?: Azilsartan medoxomil
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 328 participants
Where: 15 sitesSouth Korea
Study dates: Jul 2014to Feb 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
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.
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.
Is male or female aged ≥19 years.
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.
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.

Who cannot join

Has received any investigational compound within 30 days prior to the first dose of study medication.
Has received TAK-491 in a previous clinical study or as a therapeutic agent.
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.
Has sitting trough clinic diastolic blood pressure (DBP) greater than 114 mm Hg at Day 1 (after placebo run-in).
Has a history of hypersensitivity to TAK-491 (azilsartan medoxomil), any of its excipients, or other angiotensin-converting enzyme (ARBs).
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.

Show all 20Show fewer

Has clinically significant cardiac conduction defects (e.g., 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation, or flutter).
Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease and hypertrophic obstructive cardiomyopathy (HOCM).
Has secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing syndrome).
Is noncompliant (less than 70% or greater than 130%) with study medication during placebo run-in period.
Has severe renal dysfunction or disease (confirmed by calculated creatinine clearance <30 mL/min/1.73m^2) at Screening.
Has known or suspected unilateral or bilateral renal artery stenosis.
Has a history of drug or alcohol abuse within the past 2 years.
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.)
Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c]>8.0%) at Screening.
Has an alanine aminotransferase (ALT) level greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
Has hyperkalemia (defined as serum potassium greater than the upper limit of normal per the central laboratory) at Screening.
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.
Is required to take excluded medications.
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.

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

South Korea15 sites

Study site
Anyang-si, Gyeonggi-do
Study site
Busan
Study site
Chuncheon, Gangwon-do
Study site
Daegu, Gyeongsangbuk-do
Study site
Daegu
Study site
Daejeon
Study site
Goyang-si, Gyeonggi-do
Study site
Gwangju, Jeollanam-do
Study site
Incheon
Study site
Jeonju, Jeollabuk-do
Study site
Seongnam-si, Gyeonggi-do
Study site
Seoul
Study site
Suwon, Gyeonggi-do
Study site
Wŏnju, Gangwon-do
Study site
Yangsan, Gyeongsangnam-do

Other trials in South Korea

About this study

Official title: 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.

Read the 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.

Conditions: Hypertension
Being tested: Azilsartan medoxomil, Azilsartan medoxomil placebo
Keywords: Drug therapy
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Azilsartan medoxomilDrug
Also called TAK-491
Azilsartan medoxomil tablets
Azilsartan medoxomil placeboDrug
Azilsartan medoxomil placebo-matching tablets

Study groups in NCT02203916
Study group	Role	What they receive
Azilsartan Medoxomil 40 mg	Experimental	Azilsartan medoxomil 40 mg, tablets, orally, once daily for 6 weeks. Receives: Drug: Azilsartan medoxomil
Azilsartan Medoxomil 80 mg	Experimental	Azilsartan medoxomil 80 mg, tablets, orally, once daily for 6 weeks. Receives: Drug: Azilsartan medoxomil
Placebo	Placebo comparator	Azilsartan medoxomil placebo-matching tablets, orally, once daily for 6 weeks. Receives: Drug: Azilsartan medoxomil placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 6

Secondary outcomes (4)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2014Feb 2016

First posted30 Jul 2014 (estimated)
Study startJul 2014
Primary completionJan 2016
Study completionFeb 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 328 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02203916
Sponsor's protocol ID: TAK-491_307
Other IDs: U1111-1130-9186
Status last verified: Oct 2016
First submitted: 28 Jul 2014
Last updated: 19 Dec 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 29445520

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-491 in Korean Subjects With Essential Hypertension
ClinicalTrials.gov ID: NCT02203916
Acronym / sponsor ID: TAK-491_307
Conditions: Hypertension
Keywords: Drug therapy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 328 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Jul 2014
Primary completion: Jan 2016 (actual)
Study completion: Feb 2016 (actual)
First posted: 30 Jul 2014 (estimated)
Results: Posted 19 Dec 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Azilsartan Medoxomil 40 mg	Experimental	Drug: Azilsartan medoxomilAzilsartan medoxomil 40 mg, tablets, orally, once daily for 6 weeks.
Azilsartan Medoxomil 80 mg	Experimental	Drug: Azilsartan medoxomilAzilsartan medoxomil 80 mg, tablets, orally, once daily for 6 weeks.
Placebo	Placebo comparator	Drug: Azilsartan medoxomil placeboAzilsartan medoxomil placebo-matching tablets, orally, once daily for 6 weeks.

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
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.
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.
Is male or female aged ≥19 years.
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.

Key exclusion criteria (20 listed)

Has received any investigational compound within 30 days prior to the first dose of study medication.
Has received TAK-491 in a previous clinical study or as a therapeutic agent.
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.
Has sitting trough clinic diastolic blood pressure (DBP) greater than 114 mm Hg at Day 1 (after placebo run-in).
Has a history of hypersensitivity to TAK-491 (azilsartan medoxomil), any of its excipients, or other angiotensin-converting enzyme (ARBs).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Azilsartan medoxomilAlso: TAK-491Azilsartan medoxomil tablets	Drug	Azilsartan Medoxomil 40 mg, Azilsartan Medoxomil 80 mg
Azilsartan medoxomil placeboAzilsartan medoxomil placebo-matching tablets	Drug	Placebo

Primary outcome

Change From Baseline to Week 6 in Trough Clinic Sitting Systolic Blood Pressure (SBP)
Time frame: Baseline and Week 6
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.

4 secondary outcomes

Change From Baseline to Week 6 in Trough Clinic Sitting Diastolic Blood Pressure (DBP)
Time frame: Baseline and Week 6
Percentage of Participants Who Achieved a Clinic DBP Response at Week 6
Time frame: Baseline and Week 6
Percentage of Participants Who Achieved a Clinic SBP Response at Week 6
Time frame: Baseline and Week 6
Percentage of Participants Who Achieved Both a Clinic DBP and SBP Response at Week 6
Time frame: Baseline and Week 6

Results and safety

Results posted to the registry on 19 Dec 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	65	57
Azilsartan Medoxomil 40 mg	132	122
Azilsartan Medoxomil 80 mg	131	120

Primary outcome: Change From Baseline to Week 6 in Trough Clinic Sitting Systolic Blood Pressure (SBP)

Time frame: Baseline and Week 6. Least squares mean (Standard Error). Unit: mmHg

Measure	Placebo n = 63	Azilsartan Medoxomil 40 mg n = 127	Azilsartan Medoxomil 80 mg n = 129
Value	-8.776 (2.0039)	-22.093 (1.4117)	-23.731 (1.4017)

Placebo vs Azilsartan Medoxomil 40 mg: LS Mean Difference: -13.317 (95% CI -18.138 to -8.497), p <0.001, ANCOVA
Placebo vs Azilsartan Medoxomil 80 mg: LS Mean Difference: -14.955 (95% CI -19.770 to -10.141), p <0.001, ANCOVA

Population analysed: Participants from the Full Analysis Set (FAS), including all randomized participants, who received at least 1 dose of double-blind study drug, with both a Baseline value and at least 1 post-baseline value, who were randomized only once. Missing values were imputed using last observation carried forward (LOCF).

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events: from the first dose of double-blind study drug to 14 days after the last dose (up to 66 days). Serious adverse events: from the first dose of double blind study drug to 30 days after the last dose (up to 82 days).. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 65 (0%)	7 of 65 (10.8%)	Not reported
Azilsartan Medoxomil 40 mg	0 of 132 (0%)	8 of 132 (6.1%)	Not reported
Azilsartan Medoxomil 80 mg	2 of 130 (1.5%)	14 of 130 (10.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29445520Juhasz 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director Clinical Science study director

Takeda

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azilsartan medoxomil in people with Hypertension, run by Takeda at 15 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 6 in Trough Clinic Sitting Systolic Blood Pressure (SBP) (time frame: Baseline and Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02203916, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2016.