CClinicalTrials.gg
Sign In
CompletedNCT00760214Updated Nov 15, 2012Results posted

Efficacy and Safety Study of Azilsartan Medoxomil Compared to Ramipril for Treating Essential Hypertension

A Phase 3 interventional study of Azilsartan medoxomil and Azilsartan medoxomil in Hypertension, sponsored by Takeda. Completed at 72 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-11-15.

Sponsored by Takeda · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
885
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil, once daily (QD), compared to ramipril for treating Essential Hypertension.

Read the detailed description

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system, a system of hormone-mediated feedback interactions that results in the relaxation or constriction of blood vessels in response to various stimuli. Angiotensin II, a polypeptide hormone, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme as part of the renin-angiotensin-aldosterone system. Angiotensin II is the principal pressor agent of the renin-angiotensin-aldosterone system with a myriad of effects on the cardiovascular system and on electrolyte homeostasis. Two receptors for angiotensin II have been identified. Angiotensin II type 1 receptors are located predominantly in vascular smooth muscle, where activation by angiotensin II results in vasoconstriction, hypertrophic proliferation, and inflammation. In contrast, stimulation of angiotensin II type 2 receptors by angiotensin II results in vasodilatation, antiproliferative effects that are opposite from those of angiotensin II type 1 receptor stimulation.

Drugs that modulate the renin-angiotensin-aldosterone system are used commonly worldwide for the treatment of hypertension. Of these, some block the synthesis of angiotensin II by inhibiting angiotensin-converting enzymes, while others inhibit the action of angiotensin II by binding directly to the angiotensin II type 1 receptor (called angiotensin II receptor blockers), thereby causing vasodilatation of blood vessels, resulting in a reduction in blood pressure. The effects of angiotensin II receptor blockers on other conditions in which the renin-angiotensin-aldosterone system plays a significant role, such as congestive heart failure, postmyocardial infarction management and diabetic nephropathy have also been investigated.

Although antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. Angiotensin-converting enzyme inhibitors are commonly associated with cough and more rarely with angioedema. Beta-blockers are associated with fatigue and erectile dysfunction, calcium antagonists with peripheral edema and diuretics with metabolic complications. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of hypertensive agents, although there is still a need for compounds with improved tolerability and efficacy for the treatment of hypertension.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker with high affinity for, and selective antagonistic activity at, the angiotensin II type 1 receptor, and is being developed for clinical use as an antihypertensive agent.

Ramipril is an angiotensin-converting enzyme inhibitor widely prescribed in Europe and Asia for the treatment of mild to moderate essential hypertension.

This study is designed to compare the efficacy and safety/tolerability of azilsartan medoxomil and ramipril for the treatment of hypertension.

Participants in this study will be seen twice during the first month, then once a month for five months. Participants will also be required to fast for 8 hours prior to each visit to the study center. Total duration of study participation is 24-weeks, plus a safety follow up phone call after the study has ended.

02

Conditions studied

  • Hypertension

Keywords

  • Essential Hypertension
  • Hypertension
  • Drug Therapy
  • Blood Pressure, High
  • Vascular Disease
  • Cardiovascular Disease
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 885 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
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg, inclusive).
  2. A female participant of childbearing potential who is sexually active agrees to use adequate contraception from screening throughout the duration of the study, and cannot be pregnant.
  3. Has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory at Screening or the results are deemed not clinically significant for inclusion into this study by the investigator.
  4. Is willing to discontinue current antihypertensive medications at Screening Day -21. If the participant is on amlodipine prior to screening, the participant is willing to discontinue this medication at Screening Day -28.

Exclusion criteria

Exclusion Criteria:

  1. Has an systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 114 mmHg at Randomization.
  2. Is taking or expected to take an excluded medication including antihypertensive agents, insulin or other agents that alter blood pressure.
  3. Is hypersensitive to angiotensin II receptor blockers and/or angiotensin-converting enzyme inhibitors.
  4. Has a recent history within the last 6 months of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
  5. Has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).
  6. Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
  7. Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
  8. Is noncompliant (less than 70% or greater than 130%) with study medication during placebo run-in period.
  9. Has severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL/min/1.73 m² at Screening).
  10. Has known or suspected unilateral or bilateral renal artery stenosis.
  11. Has a history of drug or alcohol abuse within the past 2 years.
  12. Has a previous 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 participants with basal cell or stage I squamous cell carcinoma of the skin).
  13. Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c greater than 8.0%) or is taking insulin.
  14. Has hyperkalemia as defined by the central laboratory normal reference range at Screening.
  15. Has an upper arm circumference less than 24 cm or greater than 42 cm.
  16. Works night (third) shift (defined as 11 PM to 7 AM).
  17. Has an alanine aminotransferase level at Screening of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
  18. Is currently participating in another investigational study or has participated in an investigational study within 30 days prior to Screening.
  19. Has any other serious disease or condition at Screening or Randomization that would compromise participant's safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.
  20. Has been randomized in a previous azilsartan medoxomil study.
05

Study design

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

Study arms

  • Experimental
    Azilsartan Medoxomil 40 mg QD

    Drug: Azilsartan medoxomil

  • Experimental
    Azilsartan Medoxomil 80 mg QD

    Drug: Azilsartan medoxomil

  • Active comparator
    Ramipril 10 mg QD

    Drug: Ramipril

Interventions

  • DrugAzilsartan medoxomil

    Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.

    Also known as: TAK-491, Edarbi

  • DrugAzilsartan medoxomil

    Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.

    Also known as: TAK-491, Edarbi

  • DrugRamipril

    Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.

    Also known as: Tritace, Ramace, Altace

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.

    The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

    Time frame: Baseline and Week 24.

Secondary outcomes

  1. Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure

    The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

    Time frame: Baseline and Week 24.

  2. Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in 24-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

    Time frame: Baseline and Week 24.

  3. Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in 24-hour mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

    Time frame: Baseline and Week 24.

  4. Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring

    The change in the 12-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

    Time frame: Baseline and Week 24.

  5. Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring

    The change in the 12-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

    Time frame: Baseline and Week 24.

  6. Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

    Time frame: Baseline and Week 24.

  7. Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

    Time frame: Baseline and Week 24.

  8. Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

    Time frame: Baseline and Week 24.

  9. Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

    Time frame: Baseline and Week 24.

  10. Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in trough mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

    Time frame: Baseline and Week 24.

  11. Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in trough mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

    Time frame: Baseline and Week 24.

07

Results

Posted Apr 19, 2011

Participant flow

Participants enrolled at 122 investigative sites in Bulgaria, Estonia, Finland, Germany, the Netherlands, Poland, Russia, Serbia and Montenegro, Slovakia and Sweden from 24 January 2008 to 21 April 2009.

Participant flow — Overall Study
MilestoneAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Started295294296
Completed265264255
Not completed303041
Withdrew: Adverse event8912
Withdrew: Protocol violation303
Withdrew: Lost to follow-up001
Withdrew: Withdrawal by subject121413
Withdrew: Lack of efficacy324
Withdrew: Pregnancy001
Withdrew: Physician decision111
Withdrew: Other346

Outcome measures

PrimaryChange From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.

The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.-20.63 ± 0.946-21.24 ± 0.949-12.22 ± 0.948
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented. Overall 0.05 level of significance for multiple comparisons controlled using stepwise testing procedure.) · Mean difference (final values): -8.41 · 95% CI -11.04 to -5.78
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented. Overall 0.05 level of significance for multiple comparisons controlled using stepwise testing procedure.) · Mean difference (final values): -9.03 · 95% CI -11.66 to -6.39
SecondaryChange From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure

The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure-10.18 ± 0.553-10.54 ± 0.556-4.87 ± 0.555
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -5.31 · 95% CI -6.85 to -3.78
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -5.66 · 95% CI -7.21 to -4.12
SecondaryChange From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in 24-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-12.65 ± 1.006-12.29 ± 0.992-7.83 ± 1.022
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -4.82 · 95% CI -7.64 to -2.01
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.002 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -4.47 · 95% CI -7.27 to -1.66
SecondaryChange From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in 24-hour mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-8.03 ± 0.655-8.32 ± 0.646-5.26 ± 0.666
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.003 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -2.77 · 95% CI -4.61 to -0.94
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -3.06 · 95% CI -4.89 to -1.24
SecondaryChange From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring

The change in the 12-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring-12.06 ± 1.103-11.71 ± 1.087-8.28 ± 1.121
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.017 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -3.77 · 95% CI -6.87 to -0.68
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.029 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -3.43 · 95% CI -6.50 to -0.36
SecondaryChange From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring

The change in the 12-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring-7.71 ± 0.743-8.07 ± 0.732-5.65 ± 0.755
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.052 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -2.06 · 95% CI -4.15 to 0.02
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.022 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -2.42 · 95% CI -4.49 to -0.35
SecondaryChange From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-12.61 ± 1.047-12.35 ± 1.032-8.08 ± 1.064
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.003 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -4.53 · 95% CI -7.46 to -1.59
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.004 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -4.26 · 95% CI -7.18 to -1.35
SecondaryChange From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-8.19 ± 0.700-8.53 ± 0.689-5.55 ± 0.711
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.008 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -2.64 · 95% CI -4.60 to -0.68
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.003 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -2.98 · 95% CI -4.93 to -1.04
SecondaryChange From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-12.82 ± 1.135-12.69 ± 1.115-6.87 ± 1.147
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -5.95 · 95% CI -9.12 to -2.77
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -5.82 · 95% CI -8.96 to -2.67
SecondaryChange From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-7.44 ± 0.764-8.20 ± 0.750-4.43 ± 0.773
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = 0.006 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -3.01 · 95% CI -5.15 to -0.88
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -3.77 · 95% CI -5.89 to -1.65
SecondaryChange From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in trough mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-15.60 ± 1.172-14.93 ± 1.151-6.73 ± 1.186
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -8.87 · 95% CI -12.15 to -5.60
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -8.20 · 95% CI -11.46 to -4.95
SecondaryChange From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

The change in trough mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

Time frame:
Baseline and Week 24.
Reported as:
Least squares mean · mmHg
Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
mmHgAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.-10.21 ± 0.898-9.85 ± 0.883-4.53 ± 0.909
Statistical analysis
  • Azilsartan Medoxomil 40 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -5.68 · 95% CI -8.19 to -3.17
  • Azilsartan Medoxomil 80 mg QD vs Ramipril 10 mg QD · ANCOVA · p = <.001 (Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.) · Mean difference (final values): -5.32 · 95% CI -7.81 to -2.82

Adverse events

Collected over Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Azilsartan Medoxomil 40 mg QD—8/294 (2.7%)22/294 (7.5%)
Azilsartan Medoxomil 80 mg QD—12/293 (4.1%)16/293 (5.5%)
Ramipril 10 mg QD—6/293 (2%)36/293 (12.3%)
Most frequent serious events
Showing 10 of 23
Most frequent serious events
EventAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
Atrial fibrillationCardiac disorders1/2942/2931/293
Acute coronary syndromeCardiac disorders0/2940/2931/293
Angina pectorisCardiac disorders0/2941/2930/293
HydroceleCongenital, familial and genetic disorders0/2941/2930/293
Retinal detachmentEye disorders0/2941/2930/293
Salivary gland calculusGastrointestinal disorders0/2941/2930/293
AppendicitisInfections and infestations1/2940/2931/293
Hepatitis CInfections and infestations1/2940/2931/293
UrosepsisInfections and infestations1/2940/2931/293
Upper respiratory tract infectionInfections and infestations0/2941/2930/293
Most frequent other events
Most frequent other events
EventAzilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QD
CoughRespiratory, thoracic and mediastinal disorders3/2944/29324/293
NasopharyngitisInfections and infestations19/29413/29317/293

Baseline characteristics

Age, Customized
Age, Customized(Participants)Azilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QDTotal
<45 years404530115
Between 45 and 64 years166168195529
≥65 years898170240
Sex: Female, Male
Sex: Female, Male(Participants)Azilsartan Medoxomil 40 mg QDAzilsartan Medoxomil 80 mg QDRamipril 10 mg QDTotal
Female136136149421
Male159158146463
08

Study locations

72 sites
  • Pleven, Bulgaria
  • Plovdiv, Bulgaria
  • Rouse, Bulgaria
  • Sofia, Bulgaria
  • Varna, Bulgaria
  • Paide, Estonia
  • Tallinn, Estonia
  • Tartu, Estonia
  • Viljandi, Estonia
  • Joensuu, Finland
  • Mikkeli, Finland
  • Tampere, Finland
  • Turku, Finland
  • Augsburg, Germany
  • Bad Krozingen, Germany
  • Bad Segeberg, Germany
  • Berlin, Germany
  • Dortmund, Germany
  • Dresden, Germany
  • Essen, Germany
  • Frankfurt, Germany
  • Goch, Germany
  • Grossheirath, Germany
  • Hamburg, Germany
  • Karlsruhe, Germany
  • Koeln, Germany
  • Kuenzing, Germany
  • Leipzig, Germany
  • Luebeck, Germany
  • Mannheim, Germany
  • Muenchen, Germany
  • Nuernberg, Germany
  • Siegen, Germany
  • Deurne, Netherlands
  • Ewijk, Netherlands
  • Geleen, Netherlands
  • Lichtenvoorde, Netherlands
  • Oude Pekela, Netherlands
  • Rijswijk, Netherlands
  • Roelofarendsveen, Netherlands
  • Rotterdam, Netherlands
  • Wildervank, Netherlands
  • Gdansk, Poland
  • Gniewkowo, Poland
  • Kamieniec Zabkowicki, Poland
  • Katowice, Poland
  • Libiaz, Poland
  • Lodz, Poland
  • Olawa, Poland
  • Plock, Poland
  • Poznan, Poland
  • Skierniewice, Poland
  • Tarnow, Poland
  • Moscow, Russian Federation
  • Perm, Russian Federation
  • St Petersburg, Russian Federation
  • Belgrade, Serbia
  • Niska Banja, Serbia
  • Nis, Serbia
  • Zemun, Serbia
  • Bratislava, Slovakia
  • Galanta, Slovakia
  • Levice, Slovakia
  • Lucenec, Slovakia
  • Rimavska Sobota, Slovakia
  • Boden, Sweden
  • Göteborg, Sweden
  • Luleå, Sweden
  • Lund, Sweden
  • Malmö, Sweden
  • Skene, Sweden
  • Örebro, Sweden
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 15, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00760214
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Sep 26, 2008
Start date
Jan 2008
Primary completion
Apr 2009
Completion
Apr 2009
Results posted
Apr 19, 2011
Last update
Nov 15, 2012

Study contacts

Medical Director
study director · Takeda Global Research & Development Center (Europe), Ltd.

Oversight

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

Not currently enrolling

This study is completed, as verified in Nov 2012. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Hypertension→

Other studies from this sponsor

Takeda

Start the discussion