Azilsartan Medoxomil (TAK-491) Compared to Valsartan in Chinese Participants With Hypertension
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT02480764
Collaborator
(none)
612
30
3
25.6
20.4
0.8
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the antihypertensive effect of azilsartan medoxomil compared with valsartan in Chinese participants with essential hypertension.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The drug being tested in this study is called TAK-491 (azilsartan medoxomil). Azilsartan medoxomil is being tested to treat Chinese people who have essential hypertension. This study will look at change in blood pressure after 8 weeks of treatment in people who take azilsartan medoxomil compared to people who take valsartan.
The study enrolled 612 patients. Prior to the start of study treatment, participants who have not received antihypertensive treatment within 28 days participated in a 2-week -run in period. Upon completion of the run-in period, participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which 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
-
Valsartan 160 mg
All participants were asked to take study medication at the same time each day throughout the study.
This multi-centre trial was conducted in China. The overall time to participate in this study is up to 14 weeks. Participants made 9 visits to the clinic and contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
Study Design
Study Type:
Interventional
Actual Enrollment
:
612 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Double-Blind, Randomized, Parallel-Group Study to Compare the Efficacy and Safety of TAK-491 With Valsartan in Chinese Subjects With Essential Hypertension
Actual Study Start Date
:
Aug 27, 2015
Actual Primary Completion Date
:
Sep 22, 2017
Actual Study Completion Date
:
Oct 13, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Azilsartan medoxomil 40 mg Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. |
Drug: Azilsartan medoxomil
Azilsartan medoxomil tablets
Other Names:
Drug: Azilsartan medoxomil Placebo
Azilsartan medoxomil placebo-matching tablets
Drug: Valsartan Placebo
Valsartan placebo-matching capsules
|
| Experimental: Azilsartan medoxomil 80 mg Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. |
Drug: Azilsartan medoxomil
Azilsartan medoxomil tablets
Other Names:
Drug: Azilsartan medoxomil Placebo
Azilsartan medoxomil placebo-matching tablets
Drug: Valsartan Placebo
Valsartan placebo-matching capsules
|
| Active Comparator: Valsartan 160 mg Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
Drug: Valsartan
Valsartan 80 mg capsules
Other Names:
Drug: Azilsartan medoxomil Placebo
Azilsartan medoxomil placebo-matching tablets
Drug: Valsartan Placebo
Valsartan placebo-matching capsules
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure (SBP) [Baseline and Week 8]
The change in trough clinic sitting SBP measured at Week 8 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting SBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
Secondary Outcome Measures
- Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure (DBP) [Baseline and Week 8]
The change in trough clinic sitting DBP measured at Week 8 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting DBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
- Percentage of Participants Who Achieved a Clinic SBP Response at Week 8 [Week 8]
Clinic SBP response was defined as clinic SBP <140 mm Hg and/or reduction of ≥20 mm Hg from Baseline. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
- Percentage of Participants Who Achieved a Clinic DBP Response at Week 8 [Week 8]
Clinic DBP response was defined as clinic DBP <90 mm Hg and/or reduction of ≥10 mm Hg from Baseline. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
- Percentage of Participants Who Achieved Both Clinic SBP and DBP Response at Week 8 [Week 8]
Clinic SBP response was defined as clinic SBP <140 mm Hg and/or reduction of ≥20 mm Hg from Baseline and clinic DBP response was defined as clinic DBP <90 mm Hg and/or reduction of ≥10 mm Hg from Baseline. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
- Percentage of Participants Who Achieved Target Clinic SBP <140 mm Hg, Clinic DBP <90 mm Hg or Both at Week 8 [Week 8]
Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
- Percentage of Participants Who Achieved Target Clinic SBP <130 mm Hg, Target Clinic DBP <80 mm Hg or Both at Week 8 [Week 8]
Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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 participant 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 a man or woman aged 18 years or older.
-
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.
-
A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent through 30 days after last study drug dose.
-
Has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
-
Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if the participant is on amlodipine or chlorthalidone.
Exclusion Criteria:
-
Has a mean, sitting clinic diastolic blood pressure (DBP) greater than 110 mm Hg at Day 1 (after placebo run in).
-
Is non-compliant (less than 70% or greater than 130%) with study medication during placebo run-in period.
-
Has secondary hypertension of any etiology (eg, renovascular disease documented as the cause of hypertension, pheochromocytoma, Cushing's syndrome).
-
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.
-
Has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, sick sinus syndrome).
-
Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease and hypertrophic obstructive cardiomyopathy (HOCM).
-
Has severe renal dysfunction or disease (based on estimated glomerular filtration rate [GFR] <30 mL/min/1.73 m^2) at Screening.
-
Has known or suspected unilateral or bilateral renal artery stenosis.
-
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 participants with basal cell or Stage 1 squamous cell carcinoma of the skin).
-
Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c]
8.5%) at Screening.
-
Has hyperkalemia (defined as serum potassium above the normal reference range of the central laboratory) at Screening.
-
Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of greater than 2.5 times the upper limit of normal (ULN), active liver disease, or jaundice at Screening.
-
Has any other known 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.
-
Has a history of hypersensitivity or allergies to TAK-491 (azilsartan medoxomil), any of its excipients or other angiotension II (AII) receptor blockers (ARBs).
-
If female, the participant 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.
-
Is currently participating in another investigational study or is receiving or has received any investigational compound within 30 days prior to the first dose of study medication.
Note: This criterion does not apply to participants who participated in observational studies that lacked an intervention or invasive procedure.
-
Is an immediate family member, study site employee, or is in a dependant 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 a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within the past 2 years.
-
Is taking or expected to take an excluded medication.
-
Works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]). (Only for participants with ambulatory blood pressure monitoring [ABPM].)
-
Has an upper arm circumference <24 cm or >42 cm. (Only for participants with ABPM.)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Chao Yang Hospital | Beijing | Beijing | China | 100020 |
| 2 | Beijing Anzhen Hospital | Beijing | Beijing | China | 100029 |
| 3 | Beijing Friendship Hospital, Capital Medical University | Beijing | Beijing | China | 100050 |
| 4 | Beijing Tong Ren Hospital, Capital Medical University | Beijing | Beijing | China | 100730 |
| 5 | Fujian Medical University Union Hospital | Fuzhou | Fujian | China | 350001 |
| 6 | Fujian Provincial Hospital | Fuzhou | Fujian | China | 350001 |
| 7 | The First Affiliated Hospital of Fujian Medical University | Fuzhou | Fujian | China | 350005 |
| 8 | Guangdong General Hospital | Guangzhou | Guangdong | China | 510080 |
| 9 | The First Affiliated Hospital, Sun Yat-sen University | Guangzhou | Guangdong | China | 510080 |
| 10 | The Peoples Hospital of Guangxi Zhuang Autonomous Region | Nanning | Guangxi | China | 530021 |
| 11 | Affiliated Hospital of Hainan Medical University. | Haikou | Hainan | China | 570102 |
| 12 | Hebei Cangzhou Central Hospital | Cangzhou | Hebei | China | 061001 |
| 13 | The 4th Hospital of Hebei Medical University | Shijiazhuang | Hebei | China | 50011 |
| 14 | Hunan Province People's Hospital | Changsha | Hunan | China | 410002 |
| 15 | The Third Xiangya Hospital of Central South University | Changsha | Hunan | China | 410013 |
| 16 | Zhuzhou Central Hospital | Fuzhou | Hunan | China | 421003 |
| 17 | Cardiology/Zhong Da Hospital, Southeast University | Nanjing | Jiangsu | China | 210009 |
| 18 | Nanjing Medical University Affiliated 2nd Hospital | Nanjing | Jiangsu | China | 210011 |
| 19 | The Affiliated Hospital of Xuzhou Medical College | Xuzhou | Jiangsu | China | 221002 |
| 20 | Affiliated Hospital of Jiangsu University | Zhenjiang | Jiangsu | China | 212001 |
| 21 | The First Affiliated Hospital of NanChang University | Nanchang | Jiangxi | China | 330006 |
| 22 | China-Japan Union Hospital of Jilin University | Changchun | Jilin | China | 130031 |
| 23 | People's Hospital of Liaoning Province | Shenyang | Liaoning | China | 110015 |
| 24 | Shanghai Changzheng Hospital | Shanghai | Shanghai | China | 200003 |
| 25 | Shanghai East Hospital | Shanghai | Shanghai | China | 200120 |
| 26 | Cardiology/The Second Hospital of Shanxi Medical University | Taiyuan | Shanxi | China | 030001 |
| 27 | First Affiliated Hospital of Xian Jiaotong University | Xi'an | Shanxi | China | 710061 |
| 28 | Tianjin People's Hospital | Tianjin | Tianjin | China | 300121 |
| 29 | Tianjin Third Central Hospital | Tianjin | Tianjin | China | 300170 |
| 30 | TEDA International Cardiovascular Hospital | Tianjin | Tianjin | China | 300457 |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02480764
Other Study ID Numbers:
- TAK-491_305
- U1111-1159-5579
First Posted:
Jun 24, 2015
Last Update Posted:
Mar 5, 2019
Last Verified:
Feb 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Takeda
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 30 investigative sites in China from 27 August 2015 to 13 October 2017. |
|---|---|
| Pre-assignment Detail | Participants with a diagnosis of hypertension were randomized at a ratio of 1:1:1 into 1 of 3 treatment groups, once a day azilsartan medoxomil 40 mg, azilsartan medoxomil 80 mg or valsartan 160 mg. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Period Title: Overall Study | |||
| STARTED | 199 | 209 | 204 |
| COMPLETED | 189 | 189 | 183 |
| NOT COMPLETED | 10 | 20 | 21 |
Baseline Characteristics
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. | Total of all reporting groups |
| Overall Participants | 199 | 209 | 204 | 612 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
57.4
(9.52)
|
57.0
(9.88)
|
56.8
(9.48)
|
57.1
(9.62)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
92
46.2%
|
94
45%
|
74
36.3%
|
260
42.5%
|
| Male |
107
53.8%
|
115
55%
|
130
63.7%
|
352
57.5%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
199
100%
|
209
100%
|
204
100%
|
612
100%
|
| Region of Enrollment (Count of Participants) | ||||
| China |
199
100%
|
209
100%
|
204
100%
|
612
100%
|
| Height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
164.3
(8.92)
|
164.2
(8.81)
|
165.3
(7.73)
|
164.6
(8.50)
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
71.75
(14.046)
|
71.60
(11.903)
|
72.79
(12.903)
|
72.05
(12.952)
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg/m^2] |
26.43
(3.784)
|
26.47
(3.436)
|
26.52
(3.444)
|
26.48
(3.550)
|
| Smoking Classification (Count of Participants) | ||||
| Participant has never smoked |
151
75.9%
|
147
70.3%
|
136
66.7%
|
434
70.9%
|
| Participant is a current smoker |
39
19.6%
|
51
24.4%
|
55
27%
|
145
23.7%
|
| Participant is an ex-smoker |
9
4.5%
|
11
5.3%
|
13
6.4%
|
33
5.4%
|
| Female Reproductive Status (Count of Participants) | ||||
| Postmenopausal |
68
34.2%
|
71
34%
|
51
25%
|
190
31%
|
| Surgically Sterile |
12
6%
|
5
2.4%
|
7
3.4%
|
24
3.9%
|
| Female of Childbearing Potential |
12
6%
|
18
8.6%
|
16
7.8%
|
46
7.5%
|
| N/A (Participant is Male) |
107
53.8%
|
115
55%
|
130
63.7%
|
352
57.5%
|
| Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mL/min/1.73m^2] |
109.50
(26.309)
|
110.45
(28.771)
|
108.00
(29.206)
|
109.32
(28.116)
|
| Baseline glycosylated haemoglobin (HbA1c) (Percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Percentage of glycosylated haemoglobin] |
5.67
(0.569)
|
5.77
(0.793)
|
5.75
(0.716)
|
5.73
(0.701)
|
Outcome Measures
| Title | Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure (SBP) |
|---|---|
| Description | The change in trough clinic sitting SBP measured at Week 8 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting SBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Baseline and Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using last observation carried forward (LOCF). Number analyzed at a visit is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Baseline SBP |
157.873
(0.5123)
|
158.236
(0.5010)
|
158.594
(0.5123)
|
| Change at Week 8 |
-22.483
(1.0258)
|
-24.236
(1.0027)
|
-20.551
(1.0258)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A test for noninferiority was done using a margin of 1.5 mm Hg. A test for significant difference was performed at 5% level. | |
| Statistical Test of Hypothesis | p-Value | 0.184 |
| Comments | Change at Week 8: P-value was calculated using analysis of covariance (ANCOVA) model, with treatment group as a fixed effect and baseline trough sitting clinic SBP as a continuous covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square Mean Difference |
| Estimated Value | -1.932 | |
| Confidence Interval |
(2-Sided) 95% -4.782 to 0.918 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4512 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A test for noninferiority was done using a margin of 1.5 mm Hg. A test for significant difference was performed at 5% level. | |
| Statistical Test of Hypothesis | p-Value | 0.010 |
| Comments | Change at Week 8: P-value was calculated using ANCOVA model, with treatment group as a fixed effect and baseline trough sitting clinic SBP as a continuous covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square Mean Difference |
| Estimated Value | -3.685 | |
| Confidence Interval |
(2-Sided) 95% -6.502 to -0.868 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4344 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure (DBP) |
|---|---|
| Description | The change in trough clinic sitting DBP measured at Week 8 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting DBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Baseline and Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF. Number analyzed at a visit is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Baseline DBP |
91.790
(0.7306)
|
91.510
(0.7145)
|
92.298
(0.7306)
|
| Change at Week 8 |
-10.101
(0.6684)
|
-11.463
(0.6538)
|
-8.641
(0.6686)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.123 |
| Comments | Change at Week 8: P-value was calculated using ANCOVA model, with treatment group as a fixed effect and baseline trough sitting clinic DBP as a continuous covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square Mean Difference |
| Estimated Value | -1.459 | |
| Confidence Interval |
(2-Sided) 95% -3.316 to 0.397 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.9455 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Change at 8 Week: P-value was calculated using ANCOVA model, with treatment group as a fixed effect and baseline trough sitting clinic DBP as a continuous covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square Mean Difference |
| Estimated Value | -2.822 | |
| Confidence Interval |
(2-Sided) 95% -4.659 to -0.985 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.9354 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieved a Clinic SBP Response at Week 8 |
|---|---|
| Description | Clinic SBP response was defined as clinic SBP <140 mm Hg and/or reduction of ≥20 mm Hg from Baseline. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Number [percentage of participants] |
67.0
33.7%
|
68.9
33%
|
69.0
33.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.548 |
| Comments | P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.877 | |
| Confidence Interval |
(2-Sided) 95% 0.571 to 1.347 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1920 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.921 |
| Comments | P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.979 | |
| Confidence Interval |
(2-Sided) 95% 0.638 to 1.501 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2136 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieved a Clinic DBP Response at Week 8 |
|---|---|
| Description | Clinic DBP response was defined as clinic DBP <90 mm Hg and/or reduction of ≥10 mm Hg from Baseline. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Number [percentage of participants] |
81.2
40.8%
|
81.6
39%
|
79.7
39.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.904 |
| Comments | P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough DBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.033 | |
| Confidence Interval |
(2-Sided) 95% 0.607 to 1.759 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2805 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.790 |
| Comments | P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough DBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.074 | |
| Confidence Interval |
(2-Sided) 95% 0.633 to 1.823 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2897 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieved Both Clinic SBP and DBP Response at Week 8 |
|---|---|
| Description | Clinic SBP response was defined as clinic SBP <140 mm Hg and/or reduction of ≥20 mm Hg from Baseline and clinic DBP response was defined as clinic DBP <90 mm Hg and/or reduction of ≥10 mm Hg from Baseline. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Number [percentage of participants] |
62.9
31.6%
|
67.0
32.1%
|
64.5
31.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.624 |
| Comments | P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.901 | |
| Confidence Interval |
(2-Sided) 95% 0.594 to 1.367 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1916 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.647 |
| Comments | P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.103 | |
| Confidence Interval |
(2-Sided) 95% 0.726 to 1.674 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2350 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieved Target Clinic SBP <140 mm Hg, Clinic DBP <90 mm Hg or Both at Week 8 |
|---|---|
| Description | Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Clinic SBP <140 mm Hg |
60.9
30.6%
|
62.6
30%
|
62.9
30.8%
|
| Clinic DBP <90 mm Hg |
77.2
38.8%
|
76.7
36.7%
|
74.6
36.6%
|
| Clinic SBP <140 mm Hg and DBP <90 mm Hg |
58.4
29.3%
|
60.2
28.8%
|
55.8
27.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.404 |
| Comments | Clinic SBP <140 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.831 | |
| Confidence Interval |
(2-Sided) 95% 0.537 to 1.284 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1846 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.768 |
| Comments | Clinic SBP <140 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.937 | |
| Confidence Interval |
(2-Sided) 95% 0.606 to 1.447 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2078 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.852 |
| Comments | Clinic DBP <90 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough DBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.051 | |
| Confidence Interval |
(2-Sided) 95% 0.620 to 1.784 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2837 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.868 |
| Comments | Clinic DBP <90 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough DBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.045 | |
| Confidence Interval |
(2-Sided) 95% 0.620 to 1.763 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2788 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.847 |
| Comments | Clinic SBP<140 mm Hg and DBP<90 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.042 | |
| Confidence Interval |
(2-Sided) 95% 0.684 to 1.590 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2244 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.460 |
| Comments | Clinic SBP<140 mm Hg and DBP<90 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.172 | |
| Confidence Interval |
(2-Sided) 95% 0.769 to 1.785 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2517 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieved Target Clinic SBP <130 mm Hg, Target Clinic DBP <80 mm Hg or Both at Week 8 |
|---|---|
| Description | Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. |
| Time Frame | Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF. |
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg |
|---|---|---|---|
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Measure Participants | 199 | 209 | 204 |
| Clinic SBP <130 mm Hg |
37.6
18.9%
|
42.7
20.4%
|
28.4
13.9%
|
| Clinic DBP <80 mm Hg |
45.2
22.7%
|
51.9
24.8%
|
37.1
18.2%
|
| Clinic SBP <130 mm Hg and DBP <80 mm Hg |
28.9
14.5%
|
33.0
15.8%
|
21.8
10.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.077 |
| Comments | Clinic SBP<130 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.487 | |
| Confidence Interval |
(2-Sided) 95% 0.958 to 2.307 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3333 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Clinic SBP<130 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.914 | |
| Confidence Interval |
(2-Sided) 95% 1.241 to 2.951 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4229 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.137 |
| Comments | Clinic DBP<80 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough DBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.427 | |
| Confidence Interval |
(2-Sided) 95% 0.893 to 2.280 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3414 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Clinic DBP <80 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough DBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.017 | |
| Confidence Interval |
(2-Sided) 95% 1.263 to 3.220 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4816 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.140 |
| Comments | Clinic SBP<130 mm Hg and DBP<80 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.424 | |
| Confidence Interval |
(2-Sided) 95% 0.891 to 2.276 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3407 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 80 mg, Valsartan 160 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | Clinic SBP<130 mm Hg and DBP<80 mm Hg: P-value was calculated using logistic regression model with treatment group as a fixed effect and baseline trough SBP as a continuous covariate. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.769 | |
| Confidence Interval |
(2-Sided) 95% 1.118 to 2.797 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4136 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||
| Arm/Group Title | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg | |||
| Arm/Group Description | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. | |||
All Cause Mortality |
||||||
| Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/199 (0.5%) | 0/209 (0%) | 0/204 (0%) | |||
Serious Adverse Events |
||||||
| Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/199 (1%) | 7/209 (3.3%) | 6/204 (2.9%) | |||
| Gastrointestinal disorders | ||||||
| Peptic ulcer haemorrhage | 0/199 (0%) | 1/209 (0.5%) | 0/204 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 0/199 (0%) | 0/209 (0%) | 1/204 (0.5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Meniscus injury | 0/199 (0%) | 1/209 (0.5%) | 0/204 (0%) | |||
| Subarachnoid haemorrhage | 1/199 (0.5%) | 0/209 (0%) | 0/204 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Musculoskeletal pain | 0/199 (0%) | 0/209 (0%) | 1/204 (0.5%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Ovarian neoplasm | 0/199 (0%) | 1/209 (0.5%) | 0/204 (0%) | |||
| Nervous system disorders | ||||||
| Lacunar infarction | 0/199 (0%) | 1/209 (0.5%) | 1/204 (0.5%) | |||
| Cerebral infarction | 0/199 (0%) | 1/209 (0.5%) | 0/204 (0%) | |||
| Cerebrovascular insufficiency | 0/199 (0%) | 0/209 (0%) | 1/204 (0.5%) | |||
| Renal and urinary disorders | ||||||
| Urate nephropathy | 0/199 (0%) | 0/209 (0%) | 1/204 (0.5%) | |||
| Ureteral cyst | 0/199 (0%) | 1/209 (0.5%) | 0/204 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 1/199 (0.5%) | 1/209 (0.5%) | 1/204 (0.5%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 80 mg | Valsartan 160 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 34/199 (17.1%) | 37/209 (17.7%) | 35/204 (17.2%) | |||
| Infections and infestations | ||||||
| Upper respiratory tract infection | 10/199 (5%) | 13/209 (6.2%) | 14/204 (6.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperlipidaemia | 14/199 (7%) | 14/209 (6.7%) | 16/204 (7.8%) | |||
| Hyperuricaemia | 8/199 (4%) | 11/209 (5.3%) | 8/204 (3.9%) | |||
| Renal and urinary disorders | ||||||
| Albuminuria | 11/199 (5.5%) | 10/209 (4.8%) | 6/204 (2.9%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02480764
Other Study ID Numbers:
- TAK-491_305
- U1111-1159-5579
First Posted:
Jun 24, 2015
Last Update Posted:
Mar 5, 2019
Last Verified:
Feb 1, 2019