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
ClinicalTrials.gov Identifier:
NCT00996281
First received: October 12, 2009
Last updated: October 15, 2012
Last verified: October 2012
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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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

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. ]

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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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:
unchecked 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.
unchecked 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.


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
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