Trial Outcomes & Findings for Azilsartan Medoxomil (TAK-491) Compared to Valsartan in Chinese Participants With Hypertension (NCT NCT02480764)

NCT ID: NCT02480764

Last Updated: 2019-03-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 612 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2019-03-05

Participant Flow

Participants took part in the study at 30 investigative sites in China from 27 August 2015 to 13 October 2017.

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.

Participant milestones

Measure	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.	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.	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.
Overall Study STARTED	199	209	204
Overall Study COMPLETED	189	189	183
Overall Study NOT COMPLETED	10	20	21

Reasons for withdrawal

Measure	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.	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.	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.
Overall Study Pretreatment Event/Adverse Event	3	6	3
Overall Study Major Protocol Deviation	1	4	3
Overall Study Lost to Follow-up	0	1	2
Overall Study Voluntary Withdrawal	6	5	10
Overall Study Lack of Efficacy	0	3	3
Overall Study Reason not Specified	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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 n=612 Participants Total of all reporting groups
Age, Continuous	57.4 years STANDARD_DEVIATION 9.52 • n=5 Participants	57.0 years STANDARD_DEVIATION 9.88 • n=7 Participants	56.8 years STANDARD_DEVIATION 9.48 • n=5 Participants	57.1 years STANDARD_DEVIATION 9.62 • n=4 Participants
Sex: Female, Male Female	92 Participants n=5 Participants	94 Participants n=7 Participants	74 Participants n=5 Participants	260 Participants n=4 Participants
Sex: Female, Male Male	107 Participants n=5 Participants	115 Participants n=7 Participants	130 Participants n=5 Participants	352 Participants n=4 Participants
Race/Ethnicity, Customized Asian	199 Participants n=5 Participants	209 Participants n=7 Participants	204 Participants n=5 Participants	612 Participants n=4 Participants
Region of Enrollment China	199 Participants n=5 Participants	209 Participants n=7 Participants	204 Participants n=5 Participants	612 Participants n=4 Participants
Height	164.3 cm STANDARD_DEVIATION 8.92 • n=5 Participants	164.2 cm STANDARD_DEVIATION 8.81 • n=7 Participants	165.3 cm STANDARD_DEVIATION 7.73 • n=5 Participants	164.6 cm STANDARD_DEVIATION 8.50 • n=4 Participants
Weight	71.75 kg STANDARD_DEVIATION 14.046 • n=5 Participants	71.60 kg STANDARD_DEVIATION 11.903 • n=7 Participants	72.79 kg STANDARD_DEVIATION 12.903 • n=5 Participants	72.05 kg STANDARD_DEVIATION 12.952 • n=4 Participants
Body Mass Index (BMI)	26.43 kg/m^2 STANDARD_DEVIATION 3.784 • n=5 Participants	26.47 kg/m^2 STANDARD_DEVIATION 3.436 • n=7 Participants	26.52 kg/m^2 STANDARD_DEVIATION 3.444 • n=5 Participants	26.48 kg/m^2 STANDARD_DEVIATION 3.550 • n=4 Participants
Smoking Classification Participant has never smoked	151 Participants n=5 Participants	147 Participants n=7 Participants	136 Participants n=5 Participants	434 Participants n=4 Participants
Smoking Classification Participant is a current smoker	39 Participants n=5 Participants	51 Participants n=7 Participants	55 Participants n=5 Participants	145 Participants n=4 Participants
Smoking Classification Participant is an ex-smoker	9 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	33 Participants n=4 Participants
Female Reproductive Status Postmenopausal	68 Participants n=5 Participants	71 Participants n=7 Participants	51 Participants n=5 Participants	190 Participants n=4 Participants
Female Reproductive Status Surgically Sterile	12 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Female Reproductive Status Female of Childbearing Potential	12 Participants n=5 Participants	18 Participants n=7 Participants	16 Participants n=5 Participants	46 Participants n=4 Participants
Female Reproductive Status N/A (Participant is Male)	107 Participants n=5 Participants	115 Participants n=7 Participants	130 Participants n=5 Participants	352 Participants n=4 Participants
Estimated Glomerular Filtration Rate (eGFR)	109.50 mL/min/1.73m^2 STANDARD_DEVIATION 26.309 • n=5 Participants	110.45 mL/min/1.73m^2 STANDARD_DEVIATION 28.771 • n=7 Participants	108.00 mL/min/1.73m^2 STANDARD_DEVIATION 29.206 • n=5 Participants	109.32 mL/min/1.73m^2 STANDARD_DEVIATION 28.116 • n=4 Participants
Baseline glycosylated haemoglobin (HbA1c)	5.67 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.569 • n=5 Participants	5.77 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.793 • n=7 Participants	5.75 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.716 • n=5 Participants	5.73 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.701 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure (SBP) Baseline SBP	157.873 mm Hg Standard Error 0.5123	158.236 mm Hg Standard Error 0.5010	158.594 mm Hg Standard Error 0.5123
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure (SBP) Change at Week 8	-22.483 mm Hg Standard Error 1.0258	-24.236 mm Hg Standard Error 1.0027	-20.551 mm Hg Standard Error 1.0258

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure (DBP) Baseline DBP	91.790 mm Hg Standard Error 0.7306	91.510 mm Hg Standard Error 0.7145	92.298 mm Hg Standard Error 0.7306
Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure (DBP) Change at Week 8	-10.101 mm Hg Standard Error 0.6684	-11.463 mm Hg Standard Error 0.6538	-8.641 mm Hg Standard Error 0.6686

SECONDARY outcome

Timeframe: Week 8

Population: FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Percentage of Participants Who Achieved a Clinic SBP Response at Week 8	67.0 percentage of participants	68.9 percentage of participants	69.0 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Percentage of Participants Who Achieved a Clinic DBP Response at Week 8	81.2 percentage of participants	81.6 percentage of participants	79.7 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Percentage of Participants Who Achieved Both Clinic SBP and DBP Response at Week 8	62.9 percentage of participants	67.0 percentage of participants	64.5 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Percentage of Participants Who Achieved Target Clinic SBP <140 mm Hg, Clinic DBP <90 mm Hg or Both at Week 8 Clinic SBP <140 mm Hg	60.9 percentage of participants	62.6 percentage of participants	62.9 percentage of participants
Percentage of Participants Who Achieved Target Clinic SBP <140 mm Hg, Clinic DBP <90 mm Hg or Both at Week 8 Clinic DBP <90 mm Hg	77.2 percentage of participants	76.7 percentage of participants	74.6 percentage of participants
Percentage of Participants Who Achieved Target Clinic SBP <140 mm Hg, Clinic DBP <90 mm Hg or Both at Week 8 Clinic SBP <140 mm Hg and DBP <90 mm Hg	58.4 percentage of participants	60.2 percentage of participants	55.8 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: FAS included all randomly assigned participants who received at least 1 dose of double-blind study drug. Missing values were imputed using LOCF.

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.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg n=199 Participants 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.	Azilsartan Medoxomil 80 mg n=209 Participants 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.	Valsartan 160 mg n=204 Participants 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.
Percentage of Participants Who Achieved Target Clinic SBP <130 mm Hg, Target Clinic DBP <80 mm Hg or Both at Week 8 Clinic SBP <130 mm Hg	37.6 percentage of participants	42.7 percentage of participants	28.4 percentage of participants
Percentage of Participants Who Achieved Target Clinic SBP <130 mm Hg, Target Clinic DBP <80 mm Hg or Both at Week 8 Clinic DBP <80 mm Hg	45.2 percentage of participants	51.9 percentage of participants	37.1 percentage of participants
Percentage of Participants Who Achieved Target Clinic SBP <130 mm Hg, Target Clinic DBP <80 mm Hg or Both at Week 8 Clinic SBP <130 mm Hg and DBP <80 mm Hg	28.9 percentage of participants	33.0 percentage of participants	21.8 percentage of participants

Adverse Events

Azilsartan Medoxomil 40 mg

Serious events: 2 serious events

Other events: 34 other events

Deaths: 1 deaths

Azilsartan Medoxomil 80 mg

Serious events: 7 serious events

Other events: 37 other events

Deaths: 0 deaths

Valsartan 160 mg

Serious events: 6 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azilsartan Medoxomil 40 mg n=199 participants at risk 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.	Azilsartan Medoxomil 80 mg n=209 participants at risk 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.	Valsartan 160 mg n=204 participants at risk 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.
Gastrointestinal disorders Peptic ulcer haemorrhage	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Infections and infestations Pneumonia	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.49% 1/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.50% 1/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.49% 1/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian neoplasm	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Nervous system disorders Lacunar infarction	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.49% 1/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Nervous system disorders Cerebral infarction	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Nervous system disorders Cerebrovascular insufficiency	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.49% 1/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Renal and urinary disorders Urate nephropathy	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.49% 1/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Renal and urinary disorders Ureteral cyst	0.00% 0/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.00% 0/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Vascular disorders Hypertension	0.50% 1/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.48% 1/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	0.49% 1/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.

Other adverse events

Measure	Azilsartan Medoxomil 40 mg n=199 participants at risk 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.	Azilsartan Medoxomil 80 mg n=209 participants at risk 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.	Valsartan 160 mg n=204 participants at risk 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.
Metabolism and nutrition disorders Hyperlipidaemia	7.0% 14/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	6.7% 14/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	7.8% 16/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Infections and infestations Upper respiratory tract infection	5.0% 10/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	6.2% 13/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	6.9% 14/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Metabolism and nutrition disorders Hyperuricaemia	4.0% 8/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	5.3% 11/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	3.9% 8/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.
Renal and urinary disorders Albuminuria	5.5% 11/199 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	4.8% 10/209 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.	2.9% 6/204 • From first dose of study drug through 14 days after the last dose of study drug (Up to Week 12) 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER