Trial Outcomes & Findings for A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension (NCT NCT00696384)

Last Updated: 2012-01-04

Results Overview

The change in sitting clinic diastolic blood pressure measured at final visit or week 32 from Double-blind Baseline/Week 26. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements. Each participant's blood pressure at the Final Visit/Week 26 of the open-label phase represented their Baseline blood pressure for the double-blind reversal phase.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

418 participants

Primary outcome timeframe

Double-blind Baseline (Week 26) and Week 32.

Results posted on

2012-01-04

Participant Flow

Participants enrolled at 51 investigative sites in Argentina, Mexico and the United States from 22 June 2007 to 08 May 2009.

All participants that completed the open-label phase were randomized into a double-blind reversal phase (to continue with azilsartan medoxomil or to placebo, in addition to any other antihypertensive medications received during the open-label phase).

Participant milestones

Participant milestones
Measure	Azilsartan Medoxomil QD - Open Label Phase All subjects initiated azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks, force-titrated to 80 mg, tablets, orally, once daily. After Week 8, chlorthalidone, 25 mg, tablets, orally, once daily was added as needed, followed by other non-ARB antihypertensive medications as needed to achieve target blood pressure (defined as \<140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) and \<130/80 mm Hg for participants with diabetes or CKD) for up to 26 weeks. Study medication could have been up-titrated only after the subject had been at the previous dose level for a minimum of 2 weeks. Study medication could only have been up- or down-titrated by 1 dose level per scheduled or unscheduled visit.	Azilsartan Medoxomil QD - Double-Blind Reversal Phase Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking), for 6 weeks.	Placebo QD - Double-Blind Reversal Phase Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg, orally once daily or other non-ARB antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Open Label Phase STARTED	418	0	0
Open Label Phase COMPLETED	299	0	0
Open Label Phase NOT COMPLETED	119	0	0
Double Blind Phase STARTED	0	148	151
Double Blind Phase COMPLETED	0	137	145
Double Blind Phase NOT COMPLETED	0	11	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Azilsartan Medoxomil QD - Open Label Phase All subjects initiated azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks, force-titrated to 80 mg, tablets, orally, once daily. After Week 8, chlorthalidone, 25 mg, tablets, orally, once daily was added as needed, followed by other non-ARB antihypertensive medications as needed to achieve target blood pressure (defined as \<140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) and \<130/80 mm Hg for participants with diabetes or CKD) for up to 26 weeks. Study medication could have been up-titrated only after the subject had been at the previous dose level for a minimum of 2 weeks. Study medication could only have been up- or down-titrated by 1 dose level per scheduled or unscheduled visit.	Azilsartan Medoxomil QD - Double-Blind Reversal Phase Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking), for 6 weeks.	Placebo QD - Double-Blind Reversal Phase Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg, orally once daily or other non-ARB antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Open Label Phase Adverse Event	27	0	0
Open Label Phase Protocol Violation	18	0	0
Open Label Phase Lost to Follow-up	24	0	0
Open Label Phase Withdrawal by Subject	37	0	0
Open Label Phase Other	6	0	0
Open Label Phase Lack of Efficacy	3	0	0
Open Label Phase Physician Decision	4	0	0
Double Blind Phase Adverse Event	0	2	2
Double Blind Phase Lost to Follow-up	0	2	1
Double Blind Phase Withdrawal by Subject	0	4	3
Double Blind Phase Lack of Efficacy	0	1	0
Double Blind Phase Physician Decision	0	2	0

Baseline Characteristics

A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Azilsartan Medoxomil QD - Open Label Phase n=418 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks, titrated to 80 mg, tablets, orally, once daily. After Week 8, chlorthalidone, 25 mg, tablets, orally, once daily as needed and other antihypertensive medications as needed to achieve target blood pressure (defined as \<140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) and \<130/80 mm Hg for participants with diabetes or CKD) for up to 26 weeks. Study medication could have been up-titrated only after participant had been at the previous dose level for a minimum of 2 weeks. Study medication could only have been up or down-titrated by 1 dose level per scheduled or unscheduled visit. Baseline characteristics of this Open Label phase population are described in the table below.
Age, Customized <45 years	21.3 percentage of participants n=5 Participants
Age, Customized Between 45 and 64 years	68.7 percentage of participants n=5 Participants
Age, Customized ≥ 65 years	10.0 percentage of participants n=5 Participants
Sex/Gender, Customized Female	210 participants n=5 Participants
Sex/Gender, Customized Male	208 participants n=5 Participants

PRIMARY outcome

Timeframe: Double-blind Baseline (Week 26) and Week 32.

Population: Full analysis set with last observation carried forward.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil QD - Double Blind Reversal Phase n=142 Participants Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking) as needed for 6 weeks.	Placebo QD - Double Blind Reversal Phase n=148 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Change From Double-blind Baseline (Week 26) in Sitting Clinic Diastolic Blood Pressure to Week 32	0.14 mmHg Standard Error 0.726	7.92 mmHg Standard Error 0.712

SECONDARY outcome

Timeframe: Double-blind Baseline (Week 26) and Week 32.

Population: Full analysis set with last observation carried forward.

The change in sitting clinic systolic blood pressure measured at final visit or week 32 from Double-blind Baseline/Week 26.. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements. Each participant's blood pressure at the Final Visit/Week 26 of the open-label phase represented their Baseline blood pressure for the double-blind reversal phase.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil QD - Double Blind Reversal Phase n=142 Participants Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking) as needed for 6 weeks.	Placebo QD - Double Blind Reversal Phase n=148 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Change From Double-blind Baseline (Week 26) in Sitting Clinic Systolic Blood Pressure to Week 32	0.59 mmHg Standard Error 1.121	12.97 mmHg Standard Error 1.098

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Safety analysis set with last observation carried forward.

The change from baseline in sitting clinic diastolic blood pressure measured at final visit or week 26.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil QD - Double Blind Reversal Phase n=418 Participants Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking) as needed for 6 weeks.	Placebo QD - Double Blind Reversal Phase Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Change From Open Label Baseline (Week 0) in Sitting Clinic Diastolic Blood Pressure to Week 26	-15.76 mmHg Standard Deviation 11.912	—

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Safety analysis set with last observation carried forward.

The change from baseline in sitting clinic systolic blood pressure measured at final visit or week 26.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil QD - Double Blind Reversal Phase n=418 Participants Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking) as needed for 6 weeks.	Placebo QD - Double Blind Reversal Phase Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Change From Open Label Baseline (Week 0) in Sitting Clinic Systolic Blood Pressure to Week 26	-23.01 mmHg Standard Deviation 20.657	—

SECONDARY outcome

Timeframe: Baseline to Week 26

Treatment-emergent adverse events defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after last dose of study drug, or within 30 days after the last dose of study drug for serious adverse event (SAE). A SAE is defined as any untoward medical occurrence that either results in death; is life-threatening; requires hospitalization; results in persistent or significant disability/incapacity; leads to a congenital anomaly/birth defect; or is an important medical event.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil QD - Double Blind Reversal Phase n=418 Participants Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking) as needed for 6 weeks.	Placebo QD - Double Blind Reversal Phase Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Number of Participants With Adverse Events During the Open-Label Phase Serious Adverse Events	8 participants	—
Number of Participants With Adverse Events During the Open-Label Phase Treatment Emergent Adverse Events	226 participants	—

SECONDARY outcome

Timeframe: Double-blind Baseline/Week 26 to Week 32

Treatment-emergent adverse events defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after last dose of study drug, or within 30 days after the last dose of study drug for SAE. A SAE is defined as any untoward medical occurrence that either results in death; is life-threatening; requires hospitalization; results in persistent or significant disability/incapacity; leads to a congenital anomaly/birth defect; or is an important medical event.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil QD - Double Blind Reversal Phase n=148 Participants Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking) as needed for 6 weeks.	Placebo QD - Double Blind Reversal Phase n=151 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks.
Number of Participants With Adverse Events in the Double-Blind Baseline Phase Serious Adverse Events	0 participants	1 participants
Number of Participants With Adverse Events in the Double-Blind Baseline Phase Treatment Emergent Adverse Events	42 participants	38 participants

Adverse Events

Azilsartan Medoxomil QD - Open Label

Serious events: 8 serious events

Other events: 60 other events

Deaths: 0 deaths

Azilsartan Medoxomil QD - Double-Blind Reversal Phase

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo QD - Double-Blind Reversal Phase

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Azilsartan Medoxomil QD - Open Label n=418 participants at risk Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks, titrated to 80 mg, tablets, orally, once daily.. After Week 8, chlorthalidone, 25 mg, tablets, orally, once daily as needed and other antihypertensive medications as needed to achieve target blood pressure (defined as \<140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) and \<130/80 mm Hg for participants with diabetes or CKD) for up to 26 weeks. Study medication could have been up-titrated only after the subject had been at the previous dose level for a minimum of 2 weeks. Study medication could only have been up- or down-titrated by 1 dose level per scheduled or unscheduled visit.	Azilsartan Medoxomil QD - Double-Blind Reversal Phase n=148 participants at risk Azilsartan medoxomil current dose (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other antihypertensive medications as needed for 6 weeks.	Placebo QD - Double-Blind Reversal Phase n=151 participants at risk Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for up to 6 weeks.
Cardiac disorders Acute coronary syndrome	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Eye disorders Diabetic retinopathy	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Eye disorders Eye haemorrhage	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Gastrointestinal disorders Pancreatitis	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Injury, poisoning and procedural complications Hip fracture	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Metabolism and nutrition disorders Dehydration	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Nervous system disorders Convulsion	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Nervous system disorders Dizziness	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Vascular disorders Hypotension	0.24% 1/418 • 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.	0.00% 0/148 • 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.	0.00% 0/151 • 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.
Vascular disorders Hypertensive crisis	0.00% 0/418 • 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.	0.00% 0/148 • 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.	0.66% 1/151 • 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.

Other adverse events

Other adverse events
Measure	Azilsartan Medoxomil QD - Open Label n=418 participants at risk Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks, titrated to 80 mg, tablets, orally, once daily.. After Week 8, chlorthalidone, 25 mg, tablets, orally, once daily as needed and other antihypertensive medications as needed to achieve target blood pressure (defined as \<140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) and \<130/80 mm Hg for participants with diabetes or CKD) for up to 26 weeks. Study medication could have been up-titrated only after the subject had been at the previous dose level for a minimum of 2 weeks. Study medication could only have been up- or down-titrated by 1 dose level per scheduled or unscheduled visit.	Azilsartan Medoxomil QD - Double-Blind Reversal Phase n=148 participants at risk Azilsartan medoxomil current dose (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other antihypertensive medications as needed for 6 weeks.	Placebo QD - Double-Blind Reversal Phase n=151 participants at risk Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other antihypertensive (if currently taking), tablets, orally, once daily for up to 6 weeks.
Nervous system disorders Headache	7.2% 30/418 • 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.	3.4% 5/148 • 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.	5.3% 8/151 • 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.
Nervous system disorders Dizziness	8.6% 36/418 • 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.	2.0% 3/148 • 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.	2.0% 3/151 • 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.

Additional Information

Sr. VP, Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: [email protected]

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