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CompletedNCT02203916Updated Dec 19, 2016Results posted

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

A Phase 3 interventional study of Azilsartan medoxomil and Azilsartan medoxomil placebo in Hypertension, sponsored by Takeda. Completed at 15 sites in Korea, Republic of. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2016-12-19.

Sponsored by Takeda · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
328
Allocation
Randomized
Ages
19 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Hypertension

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Keywords

  • Drug therapy
03

In context

Hypertension

6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.

This study's enrollment of 328 is above the median of 90 across 4,995 interventional studies indexed under Hypertension.

Browse Hypertension studies →

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
328 participants (actual)

Study arms

  • Experimental
    Azilsartan Medoxomil 40 mg

    Azilsartan medoxomil 40 mg, tablets, orally, once daily for 6 weeks.

    Drug: Azilsartan medoxomil

  • Experimental
    Azilsartan Medoxomil 80 mg

    Azilsartan medoxomil 80 mg, tablets, orally, once daily for 6 weeks.

    Drug: Azilsartan medoxomil

  • Placebo comparator
    Placebo

    Azilsartan medoxomil placebo-matching tablets, orally, once daily for 6 weeks.

    Drug: Azilsartan medoxomil placebo

Interventions

  • DrugAzilsartan medoxomil

    Azilsartan medoxomil tablets

    Also known as: TAK-491

  • DrugAzilsartan medoxomil placebo

    Azilsartan medoxomil placebo-matching tablets

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and Week 6

Secondary outcomes

  1. 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.

    Time frame: Baseline and Week 6

  2. 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.

    Time frame: Baseline and Week 6

  3. 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.

    Time frame: Baseline and Week 6

  4. 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.

    Time frame: Baseline and Week 6

07

Results

Posted Dec 19, 2016

Participant flow

Participants took part in the study at 29 investigative sites in Korea from 12 July 2014 to 03 February 2016.

Participant flow — Overall Study
MilestonePlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Started65132131
Full analysis set (fas)65132130
Safety analysis set (sas)65132130
Completed57122120
Not completed81011
Withdrew: Pretreatment event/adverse event132
Withdrew: Major protocol deviation110
Withdrew: Lost to follow-up010
Withdrew: Voluntary withdrawal338
Withdrew: Lack of efficacy300
Withdrew: Reason not specified021

Outcome measures

PrimaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Least squares mean · mmHg
Change From Baseline to Week 6 in Trough Clinic Sitting Systolic Blood Pressure (SBP)
mmHgPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Change From Baseline to Week 6 in Trough Clinic Sitting Systolic Blood Pressure (SBP)-8.776 ± 2.0039-22.093 ± 1.4117-23.731 ± 1.4017
Statistical analysis
  • Placebo vs Azilsartan Medoxomil 40 mg · ANCOVA · p = <0.001 (Overall type 1 error rate of 0.05 was controlled using principle of 'closed' testing: each pairwise comparison to placebo was conducted at 0.05 level with no p-value adjustment if hypothesis "all treatment groups equal" was first rejected at 0.05.) · Ls mean difference: -13.317 · 95% CI -18.138 to -8.497Post-baseline p-values were from an ANCOVA model with treatment as a fixed factor and baseline values as a continuous covariate.
  • Placebo vs Azilsartan Medoxomil 80 mg · ANCOVA · p = <0.001 (Overall type 1 error rate of 0.05 was controlled using principle of 'closed' testing: each pairwise comparison to placebo was conducted at 0.05 level with no p-value adjustment if hypothesis "all treatment groups equal" was first rejected at 0.05.) · Ls mean difference: -14.955 · 95% CI -19.770 to -10.141Post-baseline p-values were from an ANCOVA model with treatment as a fixed factor and baseline values as a continuous covariate.
SecondaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · mmHg
Change From Baseline to Week 6 in Trough Clinic Sitting Diastolic Blood Pressure (DBP)
mmHgPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Change From Baseline to Week 6 in Trough Clinic Sitting Diastolic Blood Pressure (DBP)-2.6 ± 8.60-10.7 ± 10.12-11.6 ± 10.12
SecondaryPercentage 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.

Time frame:
Baseline and Week 6
Reported as:
Number · percentage of participants
Percentage of Participants Who Achieved a Clinic DBP Response at Week 6
percentage of participantsPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Percentage of Participants Who Achieved a Clinic DBP Response at Week 642.983.585.3
SecondaryPercentage 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.

Time frame:
Baseline and Week 6
Reported as:
Number · percentage of participants
Percentage of Participants Who Achieved a Clinic SBP Response at Week 6
percentage of participantsPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Percentage of Participants Who Achieved a Clinic SBP Response at Week 638.163.065.9
SecondaryPercentage 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.

Time frame:
Baseline and Week 6
Reported as:
Number · percentage of participants
Percentage of Participants Who Achieved Both a Clinic DBP and SBP Response at Week 6
percentage of participantsPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Percentage of Participants Who Achieved Both a Clinic DBP and SBP Response at Week 625.462.265.9

Adverse events

Collected over 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).. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—0/65 (0%)7/65 (10.8%)
Azilsartan Medoxomil 40 mg—0/132 (0%)8/132 (6.1%)
Azilsartan Medoxomil 80 mg—2/130 (1.5%)14/130 (10.8%)
Most frequent serious events
Most frequent serious events
EventPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
Ligament sprainInjury, poisoning and procedural complications0/650/1321/130
Patella fractureInjury, poisoning and procedural complications0/650/1321/130
Road traffic accidentInjury, poisoning and procedural complications0/650/1321/130
Tibia fractureInjury, poisoning and procedural complications0/650/1321/130
Most frequent other events
Most frequent other events
EventPlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mg
DizzinessNervous system disorders0/653/1327/130
NasopharyngitisInfections and infestations3/652/1324/130
HeadacheNervous system disorders2/653/1322/130
DyspepsiaGastrointestinal disorders2/651/1321/130

Baseline characteristics

Safety Analysis Set (SAS) included all participants who received at least 1 dose of double-blind study drug and were randomized only once.

Age, Continuous
Age, Continuous(years)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Overall Study58.8 ± 10.2159.8 ± 10.7558.3 ± 11.5759.0 ± 10.97
Gender
Gender(Participants)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Female14373788
Male519593239
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Asian65132130327
Region of Enrollment
Region of Enrollment(participants)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Korea, Republic Of65132130327
Height
Height(cm)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Mean166.1 ± 8.43164.8 ± 9.09165.6 ± 8.00165.4 ± 8.53
Weight
Weight(kg)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Mean70.85 ± 9.89270.97 ± 12.63670.32 ± 13.07070.69 ± 12.291
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Mean25.64 ± 2.65326.02 ± 3.27225.50 ± 3.46025.74 ± 3.237
Smoking Classification
Smoking Classification(participants)PlaceboAzilsartan Medoxomil 40 mgAzilsartan Medoxomil 80 mgTotal
Never smoked297165165
Current smoker12222660
Ex-smoker243939102

3 further baseline measures are reported on the registry.

08

Study locations

15 sites
  • Chuncheon-Si, Gangwon-do, Korea, Republic of
  • Wonju-Si, Gangwon-do, Korea, Republic of
  • 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
  • Daegu, Gyeongsangbuk-do, Korea, Republic of
  • Yangsan-si, Gyeongsangnam-do, Korea, Republic of
  • Jeonju-si, Jeollabuk-do, Korea, Republic of
  • Gwangju, Jeollanam-do, Korea, Republic of
  • Busan, Korea, Republic of
  • Daegu, Korea, Republic of
  • Daejeon, Korea, Republic of
  • Incheon, Korea, Republic of
  • Seoul, Korea, Republic of
09

References and documents

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 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 19, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02203916
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Jul 30, 2014
Start date
Jul 2014
Primary completion
Jan 2016
Completion
Feb 2016
Results posted
Dec 19, 2016
Last update
Dec 19, 2016

Study contacts

Medical Director Clinical Science
study director · Takeda

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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