Trial Outcomes & Findings for Efficacy and Safety of Azilsartan Medoxomil, Once Daily (QD), Co-Administered With Amlodipine in Participants With Essential Hypertension (NCT NCT00591266)

NCT ID: NCT00591266

Last Updated: 2011-07-22

Results Overview

The change in 24-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 566 participants
• Primary outcome timeframe: Baseline and Week 6.
• Results posted on: 2011-07-22

Participant Flow

Participants enrolled at 65 investigative sites in Argentina, Chile, Mexico, Peru and the United States from 03 October 2007 to 03 April 2009.

Participants with uncontrolled hypertension were enrolled in one of three, once-daily (QD) treatment groups.

Participant milestones

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Overall Study STARTED	189	188	189
Overall Study COMPLETED	180	177	175
Overall Study NOT COMPLETED	9	11	14

Reasons for withdrawal

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Overall Study Adverse Event	2	2	3
Overall Study Lost to Follow-up	0	1	0
Overall Study Protocol Violation	0	0	1
Overall Study Withdrawal by Subject	6	2	5
Overall Study Lack of Efficacy	0	2	0
Overall Study Other	1	4	5

Baseline Characteristics

Efficacy and Safety of Azilsartan Medoxomil, Once Daily (QD), Co-Administered With Amlodipine in Participants With Essential Hypertension

Baseline characteristics by cohort

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=189 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=188 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=189 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Total n=566 Participants Total of all reporting groups
Age Categorical <45 years	28 participants n=5 Participants	23 participants n=7 Participants	15 participants n=5 Participants	66 participants n=4 Participants
Age Categorical Between 45 and 64 years	97 participants n=5 Participants	111 participants n=7 Participants	115 participants n=5 Participants	323 participants n=4 Participants
Age Categorical ≥65 years	64 participants n=5 Participants	54 participants n=7 Participants	59 participants n=5 Participants	177 participants n=4 Participants
Sex: Female, Male Female	99 Participants n=5 Participants	85 Participants n=7 Participants	95 Participants n=5 Participants	279 Participants n=4 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	103 Participants n=7 Participants	94 Participants n=5 Participants	287 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

The change in 24-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-24.79 mmHg Standard Error 0.757	-24.51 mmHg Standard Error 0.754	-13.60 mmHg Standard Error 0.754

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full analysis set with last observation carried forward.

The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=187 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=183 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=179 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.	-26.96 mmHg Standard Error 1.037	-25.50 mmHg Standard Error 1.048	-15.94 mmHg Standard Error 1.060

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

The change in 24-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-15.26 mmHg Standard Error 0.492	-15.43 mmHg Standard Error 0.490	-7.79 mmHg Standard Error 0.490

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full analysis set with last observation carried forward.

The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 6 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=187 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=183 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=179 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure	-12.00 mmHg Standard Error 0.602	-12.65 mmHg Standard Error 0.609	-7.07 mmHg Standard Error 0.616

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

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

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-25.42 mmHg Standard Error 0.802	-24.95 mmHg Standard Error 0.800	-13.79 mmHg Standard Error 0.799

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

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

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-15.81 mmHg Standard Error 0.535	-15.86 mmHg Standard Error 0.533	-7.82 mmHg Standard Error 0.533

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

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

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-22.75 mmHg Standard Error 0.853	-22.72 mmHg Standard Error 0.849	-13.05 mmHg Standard Error 0.848

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

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

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-13.76 mmHg Standard Error 0.606	-13.78 mmHg Standard Error 0.604	-7.50 mmHg Standard Error 0.604

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

The change in the 12-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring	-26.10 mmHg Standard Error 0.850	-25.40 mmHg Standard Error 0.847	-13.82 mmHg Standard Error 0.846

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

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

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring	-16.13 mmHg Standard Error 0.575	-15.97 mmHg Standard Error 0.574	-7.74 mmHg Standard Error 0.574

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

The change in trough mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-22.60 mmHg Standard Error 0.942	-22.67 mmHg Standard Error 0.938	-13.76 mmHg Standard Error 0.938

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full Analysis Set.

The change in trough mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=165 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=166 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=166 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.	-14.34 mmHg Standard Error 0.698	-14.93 mmHg Standard Error 0.696	-8.39 mmHg Standard Error 0.696

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full analysis set with last observation carried forward.

Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6 relative to baseline, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=187 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=183 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=179 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg	72.7 percentage of participants	71.6 percentage of participants	45.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full analysis set with last observation carried forward.

Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6 relative to baseline, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of 3 trough sitting diastolic blood pressure measurements.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=187 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=183 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=179 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg	86.1 percentage of participants	87.4 percentage of participants	65.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 6.

Population: Full analysis set with last observation carried forward.

Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6 relative to baseline, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.

Outcome measures

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=187 Participants Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=183 Participants Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=179 Participants Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response	65.8 percentage of participants	69.4 percentage of participants	43.0 percentage of participants

Adverse Events

Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Amlodipine 5 mg QD

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD n=190 participants at risk Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=188 participants at risk Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=185 participants at risk Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Infections and infestations Urinary tract infection	0.00% 0/190 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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.	0.53% 1/188 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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% 0/185 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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 Syncope	0.53% 1/190 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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% 0/188 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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% 0/185 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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.
Reproductive system and breast disorders Ovarian cyst torsion	0.00% 0/190 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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.	0.53% 1/188 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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% 0/185 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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.
General disorders Chest pain	0.00% 0/190 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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% 0/188 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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.	0.54% 1/185 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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 QD Amlodipine 5 mg QD n=190 participants at risk Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD n=188 participants at risk Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg QD n=185 participants at risk Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Nervous system disorders Headache	5.8% 11/190 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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% 10/188 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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.	5.4% 10/185 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. 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

Sr. VP, Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.com

Results disclosure agreements

• Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER