Try our beta test site

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;   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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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 
[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.
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 [1] 
[Units: Cm]
Mean (Standard Deviation)
 171.8  (8.87)   170.6  (9.96)   172.1  (9.74)   171.5  (9.53) 
[1] Height data only available for 126 participants in the Azilsartan medoxomil + chlorthalidone 40/12.5 mg treatment group.
Body Mass Index (BMI) [1] 
[Units: Kg/m^2]
Mean (Standard Deviation)
 29.63  (5.066)   29.78  (5.206)   29.52  (4.572)   29.64  (4.937) 
[1] BMI data only available for 126 participants in the Azilsartan medoxomil + chlorthalidone 40/12.5 mg treatment group.
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 m^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 


  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
  Hide 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.


  More Information
  Hide More Information

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



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01456169     History of Changes
Other Study ID Numbers: TAK-491CLD_307
2011-000220-16 ( EudraCT Number )
U1111-1119-4743 ( Registry Identifier: WHO )
11-028 ( Registry Identifier: ROCTR )
NL36272.072.11 ( Registry Identifier: CCMO )
Study First Received: October 18, 2011
Results First Received: December 26, 2013
Last Updated: March 21, 2014