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

This study has been completed.

Study NCT00696384 Information provided by Takeda Global Research & Development Center, Inc.

First Received on June 10, 2008. Last Updated on November 29, 2011 History of Changes

Results First Received: March 24, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Hypertension
Interventions:	Drug: Azilsartan medoxomil Drug: Azilsartan medoxomil, with or without chlorthalidone and other non-angiotensin II receptor blocker antihypertensive medications. Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants enrolled at 51 investigative sites in Argentina, Mexico and the United States from 22 June 2007 to 08 May 2009.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups

	Description
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.

Description

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.

Participant Flow for 2 periods

Period 1: Open Label Phase

	Azilsartan Medoxomil QD - Open Label Phase	Azilsartan Medoxomil QD - Double-Blind Reversal Phase	Placebo QD - Double-Blind Reversal Phase
STARTED	418	0	0
COMPLETED	299	0	0
NOT COMPLETED	119	0	0
Adverse Event	27	0	0
Protocol Violation	18	0	0
Lost to Follow-up	24	0	0
Withdrawal by Subject	37	0	0
Other	6	0	0
Lack of Efficacy	3	0	0
Physician Decision	4	0	0

Period 2: Double Blind Phase

	Azilsartan Medoxomil QD - Double-Blind Reversal Phase	Placebo QD - Double-Blind Reversal Phase
STARTED	148	151
COMPLETED	137	145
NOT COMPLETED	11	6
Adverse Event	2	2
Lost to Follow-up	2	1
Withdrawal by Subject	4	3
Lack of Efficacy	1	0
Physician Decision	2	0

Baseline Characteristics

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Reporting Groups

	Description
Azilsartan Medoxomil QD - Open Label Phase	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.

Description

Azilsartan Medoxomil QD - Open Label Phase

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.

Baseline Measures

	Azilsartan Medoxomil QD - Open Label Phase
Number of Participants [units: participants]	418
Age, Customized [units: participants]
<45 years	89
Between 45 and 64 years	287
≥ 65 years	42
Age, Customized [units: percentage of participants]
<45 years	21.3
Between 45 and 64 years	68.7
≥ 65 years	10.0
Gender, Customized [units: participants]
Female	210
Male	208

Outcome Measures

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1. Primary:

Change From Double-blind Baseline (Week 26) in Sitting Clinic Diastolic Blood Pressure to Week 32 [ Time Frame: Double-blind Baseline (Week 26) and Week 32. ]

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2. Secondary:

Change From Double-blind Baseline (Week 26) in Sitting Clinic Systolic Blood Pressure to Week 32 [ Time Frame: Double-blind Baseline (Week 26) and Week 32. ]

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3. Secondary:

Change From Open Label Baseline (Week 0) in Sitting Clinic Diastolic Blood Pressure to Week 26 [ Time Frame: Baseline and Week 26. ]

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4. Secondary:

Change From Open Label Baseline (Week 0) in Sitting Clinic Systolic Blood Pressure to Week 26 [ Time Frame: Baseline and Week 26. ]

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5. Secondary:

Number of Participants With Adverse Events During the Open-Label Phase [ Time Frame: Baseline to Week 26 ]

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6. Secondary:

Number of Participants With Adverse Events in the Double-Blind Baseline Phase [ Time Frame: Double-blind Baseline/Week 26 to Week 32 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com

No publications provided

Responsible Party:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00696384 History of Changes
Other Study ID Numbers:	01-06-TL-491-016, U1111-1113-9088
Study First Received:	June 10, 2008
Results First Received:	March 24, 2011
Last Updated:	November 29, 2011
Health Authority:	United States: Food and Drug Administration