A Study to Evaluate the Effectiveness and Safety of a Fixed Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With High Blood Pressure Who do Not Achieve Target Blood Pressure Following Treatment With Azilsartan Medoxomil Alone

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01456169
First received: October 18, 2011
Last updated: March 21, 2014
Last verified: March 2014
Results First Received: December 26, 2013  
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: Essential Hypertension
Interventions: Drug: Azilsartan medoxomil/placebo
Drug: Azilsartan medoxomil - chlorthalidone

  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
A total of 1754 patients were screened at 125 investigative sites in Bulgaria, Estonia, France, Germany, Hungary, Italy, Lithuania, the Netherlands, Poland, Serbia, Slovakia, Spain, Sweden, and the United Kingdom from 31 October 2011 to 24 January 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
507 participants entered the azilsartan medoxomil 40 mg Single-Blind Monotherapy Treatment Period and 395 participants were eligible to enter the Double-Blind Treatment Period and were randomly assigned to 1 of 3 active treatment arms.

Reporting Groups
  Description
Azilsartan Medoxomil 40 mg Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil + Chlorthalidone 40/25 mg Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks.

Participant Flow:   Overall Study
    Azilsartan Medoxomil 40 mg     Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg     Azilsartan Medoxomil + Chlorthalidone 40/25 mg  
STARTED     133 [1]   127 [1]   135 [1]
COMPLETED     123     122     123  
NOT COMPLETED     10     5     12  
Adverse Event                 1                 2                 7  
Major Protocol Deviation                 3                 2                 3  
Voluntary Withdrawal                 3                 0                 2  
Lack of Efficacy                 2                 0                 0  
Other                 1                 1                 0  
[1] Indicates participants who were randomized into the double-blind treatment period



  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.
Participants who were randomized into the double-blind treatment period. Baseline was defined as the last observed value while on monotherapy study drug and before the first dose of double-blind study drug.

Reporting Groups
  Description
Azilsartan Medoxomil 40 mg Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil + Chlorthalidone 40/25 mg Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks.
Total Total of all reporting groups

Baseline Measures
    Azilsartan Medoxomil 40 mg     Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg     Azilsartan Medoxomil + Chlorthalidone 40/25 mg     Total  
Number of Participants  
[units: participants]
  133     127     135     395  
Age  
[units: years]
Mean ± Standard Deviation
  57.9  ± 10.18     59.2  ± 10.72     57.7  ± 10.46     58.2  ± 10.45  
Age, Customized  
[units: participants]
       
< 45 years     13     10     12     35  
45 to < 65 years     87     79     88     254  
≥ 65 years     33     38     35     106  
Gender  
[units: participants]
       
Female     46     54     44     144  
Male     87     73     91     251  
Race/Ethnicity, Customized [1]
[units: participants]
       
American Indian or Alaska Native     1     0     1     2  
Asian     0     1     0     1  
Black or African American     1     0     0     1  
Native Hawaiian or Other Pacific Islander     0     0     1     1  
White     132     126     134     392  
Multiracial     1     0     1     2  
Region of Enrollment  
[units: participants]
       
Bulgaria     11     10     11     32  
Estonia     18     16     18     52  
France     2     1     2     5  
Germany     29     29     28     86  
Hungary     10     9     10     29  
Italy     6     4     5     15  
Lithuania     5     4     6     15  
Netherlands     4     6     5     15  
Poland     17     18     17     52  
Serbia     4     3     4     11  
Slovakia     24     24     26     74  
Spain     1     1     1     3  
Sweden     1     2     1     4  
United Kingdom     1     0     1     2  
Weight  
[units: kg]
Mean ± Standard Deviation
  87.59  ± 15.794     86.71  ± 17.037     87.39  ± 14.876     87.24  ± 15.868  
Height [2]
[units: cm]
Mean ± Standard Deviation
  171.8  ± 8.87     170.6  ± 9.96     172.1  ± 9.74     171.5  ± 9.53  
Body Mass Index (BMI) [3]
[units: kg/m^2]
Mean ± Standard Deviation
  29.63  ± 5.066     29.78  ± 5.206     29.52  ± 4.572     29.64  ± 4.937  
Smoking Classification  
[units: participants]
       
Never smoked     77     83     77     237  
Current smoker     31     25     30     86  
Ex-smoker     25     19     28     72  
Diabetes Status  
[units: participants]
       
Yes     20     27     20     67  
No     113     100     115     328  
Estimated Glomerular Filtration Rate (eGFR)  
[units: mL/min/1.73┬ám^2]
Mean ± Standard Deviation
  84.8  ± 16.41     81.5  ± 16.25     82.4  ± 16.51     82.9  ± 16.41  
Baseline eGFR Categories (mL/min/1.73 m^2)  
[units: participants]
       
30 to < 60 ml/min/1.73 m^2     11     10     11     32  
60 to < 90 ml/min/1.73 m^2     78     85     80     243  
≥ 90 ml/min/1.73 m^2     44     32     44     120  
Trough Clinic Systolic Blood Pressure (SBP)  
[units: mmHg]
Mean ± Standard Deviation
  150.7  ± 10.69     149.6  ± 11.54     149.8  ± 10.95     150.0  ± 11.04  
Trough Clinic SBP Category (mmHg)  
[units: participants]
       
<140 mmHg     16     17     17     50  
≥140 - <160 mmHg     86     87     93     266  
≥160 - <180 mmHg     31     23     25     79  
≥180 mmHg     0     0     0     0  
Trough Clinic Diastolic Blood Pressure (DBP)  
[units: mmHg]
Mean ± Standard Deviation
  89.8  ± 7.76     87.6  ± 9.31     88.8  ± 7.99     88.7  ± 8.39  
Trough Clinic DBP Categories (mmHg)  
[units: participants]
       
<90 mmHg     68     72     70     210  
≥90 mmHg     65     55     65     185  
[1] Participants could choose more than 1 category for race and those who indicated more than 1 race category were included in each category and in the Multiracial category. Thus the total number of participants may not generally add up to the total number of each group.
[2] Height data only available for 126 participants in the Azilsartan medoxomil + chlorthalidone 40/12.5 mg treatment group.
[3] BMI data only available for 126 participants in the Azilsartan medoxomil + chlorthalidone 40/12.5 mg treatment group.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure   [ Time Frame: Baseline (of the double-blind treatment period) and Week 8 ]

2.  Secondary:   Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure   [ Time Frame: Baseline and Week 8 ]

3.  Secondary:   Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8, 22-24 hours after dosing ]

4.  Secondary:   Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8, 22-24 hours after dosing ]

5.  Secondary:   Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

6.  Secondary:   Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

7.  Secondary:   Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

8.  Secondary:   Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

9.  Secondary:   Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

10.  Secondary:   Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8. ]

11.  Secondary:   Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

12.  Secondary:   Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

13.  Secondary:   Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8   [ Time Frame: Week 8 ]

14.  Secondary:   Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8   [ Time Frame: Week 8 ]

15.  Secondary:   Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8   [ Time Frame: Week 8 ]


  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 GlobalResearch and Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


No publications provided


Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01456169     History of Changes
Other Study ID Numbers: TAK-491CLD_307, 2011-000220-16, U1111-1119-4743, 11-028, NL36272.072.11
Study First Received: October 18, 2011
Results First Received: December 26, 2013
Last Updated: March 21, 2014
Health Authority: Spain: Spanish Agency of Medicines
Estonia: The State Agency of Medicine
European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
United States: Food and Drug Administration