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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
Overall Participants Analyzed 
[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 
[1] Ethnicity was only collected from U.S. sites.
Race/Ethnicity, Customized [1] 
[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 
[1] 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.
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 [1] 
[Units: Participants]
     
Yes   59   51   110 
No   359   368   727 
[1] 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.
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 


  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



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00996281     History of Changes
Other Study ID Numbers: TAK-491CLD_308
2008-008260-28 ( Registry Identifier: EudraCT )
U1111-1111-7891 ( Other Identifier: WHO )
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