Azilsartan Medoxomil (TAK-491) Compared to Valsartan in Chinese Participants With Hypertension

Essential Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02480764
• Other study ID #: TAK-491_305
• Secondary ID: U1111-1159-5579
• Status: Completed
• Phase: Phase 3
• Start date: August 27, 2015
• Est. completion date: October 13, 2017

Study information

• Verified date: February 2019
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the antihypertensive effect of azilsartan medoxomil compared with valsartan in Chinese participants with essential hypertension.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 612
• Est. completion date: October 13, 2017
• Est. primary completion date: September 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Is a man or woman aged 18 years or older.

3. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

4. 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.

5. 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.

6. 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.

7. Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if the participant is on amlodipine or chlorthalidone.

Exclusion Criteria:

1. Has a mean, sitting clinic diastolic blood pressure (DBP) greater than 110 mm Hg at Day 1 (after placebo run in).

2. Is non-compliant (less than 70% or greater than 130%) with study medication during placebo run-in period.

3. Has secondary hypertension of any etiology (eg, renovascular disease documented as the cause of hypertension, pheochromocytoma, Cushing's syndrome).

4. 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.

5. Has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, sick sinus syndrome).

6. Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease and hypertrophic obstructive cardiomyopathy (HOCM).

7. Has severe renal dysfunction or disease (based on estimated glomerular filtration rate [GFR] <30 mL/min/1.73 m^2) at Screening.

8. Has known or suspected unilateral or bilateral renal artery stenosis.

9. 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).

10. Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8.5%) at Screening.

11. Has hyperkalemia (defined as serum potassium above the normal reference range of the central laboratory) at Screening.

12. 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.

13. 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.

14. Has a history of hypersensitivity or allergies to TAK-491 (azilsartan medoxomil), any of its excipients or other angiotension II (AII) receptor blockers (ARBs).

15. 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.

16. 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.

17. 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.

18. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within the past 2 years.

19. Is taking or expected to take an excluded medication.

20. Works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]). (Only for participants with ambulatory blood pressure monitoring [ABPM].)

21. Has an upper arm circumference <24 cm or >42 cm. (Only for participants with ABPM.)

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Azilsartan medoxomil
Azilsartan medoxomil tablets
• Valsartan
Valsartan 80 mg capsules
• Azilsartan medoxomil Placebo
Azilsartan medoxomil placebo-matching tablets
• Valsartan Placebo
Valsartan placebo-matching capsules

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital	Beijing	Beijing
China	Beijing Chao Yang Hospital	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tong Ren Hospital, Capital Medical University	Beijing	Beijing
China	Hebei Cangzhou Central Hospital	Cangzhou	Hebei
China	China-Japan Union Hospital of Jilin University	Changchun	Jilin
China	Hunan Province People's Hospital	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Zhuzhou Central Hospital	Fuzhou	Hunan
China	Guangdong General Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Affiliated Hospital of Hainan Medical University.	Haikou	Hainan
China	The First Affiliated Hospital of NanChang University	Nanchang	Jiangxi
China	Cardiology/Zhong Da Hospital, Southeast University	Nanjing	Jiangsu
China	Nanjing Medical University Affiliated 2nd Hospital	Nanjing	Jiangsu
China	The Peoples Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Shanghai Changzheng Hospital	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	People's Hospital of Liaoning Province	Shenyang	Liaoning
China	The 4th Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Cardiology/The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	TEDA International Cardiovascular Hospital	Tianjin	Tianjin
China	Tianjin People's Hospital	Tianjin	Tianjin
China	Tianjin Third Central Hospital	Tianjin	Tianjin
China	First Affiliated Hospital of Xian Jiaotong University	Xi'an	Shanxi
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure (SBP)	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.	Baseline and Week 8
Secondary	Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure (DBP)	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.	Baseline and Week 8
Secondary	Percentage of Participants Who Achieved a Clinic SBP Response at 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.	Week 8
Secondary	Percentage of Participants Who Achieved a Clinic DBP Response at 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.	Week 8
Secondary	Percentage of Participants Who Achieved Both Clinic SBP and DBP Response at 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.	Week 8
Secondary	Percentage of Participants Who Achieved Target Clinic SBP <140 mm Hg, Clinic DBP <90 mm Hg or Both at 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.	Week 8
Secondary	Percentage of Participants Who Achieved Target Clinic SBP <130 mm Hg, Target Clinic DBP <80 mm Hg or Both at 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.	Week 8