Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Takeda Global Research & Development Center, Inc.

ClinicalTrials.gov Identifier:

NCT00996281

First received: October 12, 2009

Last updated: October 15, 2012

Last verified: October 2012

History of Changes

Results First Received: October 15, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Essential Hypertension
Interventions:	Drug: Azilsartan medoxomil and chlorthalidone Drug: Olmesartan medoxomil and hydrochlorothiazide

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 took part in the study at 79 investigative sites in the United States, Netherlands, Poland, the United Kingdom and Germany from 27 October 2009 to 17 November 2011.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of essential hypertension were randomized to receive open-label treatment with either Azilsartan Medoxomil and Chlorthalidone or Olmesartan Medoxomil and Hydrochlorothiazide for up to 52 weeks.

Reporting Groups

Description

Azilsartan Medoxomil and Chlorthalidone

Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.

Olmesartan Medoxomil and Hydrochlorothiazide

Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.

Participant Flow: Overall Study

	Azilsartan Medoxomil and Chlorthalidone	Olmesartan Medoxomil and Hydrochlorothiazide
STARTED	418	419
COMPLETED	287	330
NOT COMPLETED	131	89
Adverse Event	75	37
Major Protocol Deviation	6	7
Lost to Follow-up	14	16
Withdrawal by Subject	31	20
Lack of Efficacy	0	2
Other	5	7

Baseline Characteristics

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Reporting Groups

	Description
Azilsartan Medoxomil and Chlorthalidone	Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.
Olmesartan Medoxomil and Hydrochlorothiazide	Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.
Total	Total of all reporting groups

Baseline Measures

	Azilsartan Medoxomil and Chlorthalidone	Olmesartan Medoxomil and Hydrochlorothiazide	Total
Number of Participants [units: participants]	418	419	837
Age [units: years] Mean ± Standard Deviation	58.5 ± 10.79	57.6 ± 10.80	58.1 ± 10.80
Age, Customized [units: participants]
<45 years	46	48	94
45 to 64 years	251	259	510
65 to 74 years	94	93	187
≥75 years	27	19	46
Gender [units: participants]
Female	192	173	365
Male	226	246	472
Race/Ethnicity, Customized ^[1] [units: participants]
Hispanic or Latino	40	41	81
Non-Hispanic or Latino	209	205	414
Not collected	169	172	341
Missing	0	1	1
Race/Ethnicity, Customized ^[2] [units: participants]
American Indian or Alaska Native	4	5	9
Asian	4	7	11
Black or African American	72	74	146
Native Hawaiian or Other Pacific Islander	0	0	0
White	341	336	677
Multiracial	3	3	6
Region of Enrollment [units: participants]
Poland	52	54	106
United States	249	247	496
Netherlands	56	58	114
Germany	22	21	43
United Kingdom	39	39	78
Height [units: cm] Mean ± Standard Deviation	169.9 ± 10.2	169.6 ± 10.1	169.8 ± 10.1
Weight [units: kg] Mean ± Standard Deviation	91.00 ± 21.025	92.00 ± 21.727	91.50 ± 21.373
Body Mass Index (BMI) [units: kg/m^2] Mean ± Standard Deviation	31.4 ± 6.21	31.9 ± 6.63	31.7 ± 6.42
Smoking history [units: participants]
Never smoked	214	205	419
Current smoker	82	78	160
Ex-smoker	122	136	258
Diabetes Status [units: participants]
Yes	64	59	123
No	354	360	714
Estimated glomerular filtration rate [units: participants]
Moderate impairment: ≥30 and <60 ml/min/1.73 m^2	54	43	97
Mild impairment: ≥60 and <90 ml/min/1.73 m^2	275	265	540
Normal: ≥90 ml/min/1.73 m^2	87	110	197
Missing	2	1	3
Chronic Kidney Disease (CKD) status ^[3] [units: participants]
Yes	59	51	110
No	359	368	727
Systolic blood pressure [units: participants]
≥140 - < 160 mmHg	1	1	2
≥160 - < 180 mmHg	382	385	767
≥180 mm Hg	35	33	68
Diastolic blood pressure [units: participants]
< 90 mmHg	107	103	210
≥90 mmHg	311	316	627

[1]	Ethnicity was only collected from U.S. sites.
[2]	Participants could choose more than 1 category for race. Participants who choose more than 1 race category are included in each category indicated and are also included in the multiracial category.
[3]	Participants were considered to have CKD if their estimated glomerular filtration rate (GFR) was <60 mL/min/1.73 m^2 or urinary albumin:creatinine ratio (UACR) was >200 mg albumin/g creatinine at Screening.

Outcome Measures

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1. Primary:

Percentage of Participants With at Least 1 Adverse Event [ Time Frame: From Week 0 (Day 1) to Week 52. ]

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2. Secondary:

Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN) [ Time Frame: Baseline and Week 52 ]

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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: 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.

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:	NCT00996281 History of Changes
Other Study ID Numbers:	TAK-491CLD_308, 2008-008260-28, U1111-1111-7891
Study First Received:	October 12, 2009
Results First Received:	October 15, 2012
Last Updated:	October 15, 2012
Health Authority:	United States: Food and Drug Administration United Kingdom: Department of Health United Kingdom: Food Standards Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: National Health Service United Kingdom: Research Ethics Committee Netherlands: Independent Ethics Committee Netherlands: Dutch Health Care Inspectorate Netherlands: Medical Ethics Review Committee (METC) Netherlands: Medicines Evaluation Board (MEB) Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland: Ministry of Health Poland: Ministry of Science and Higher Education Austria: Agency for Health and Food Safety Austria: Ethikkommission Austria: Federal Ministry for Health and Women Austria: Federal Office for Safety in Health Care South Africa: Medicines Control Council

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