Efficacy and Safety of Azilsartan Medoxomil Used in Combination With Metformin in Participants With Hypertension and Diabetes

This study has been terminated.
(Business Decision; No Safety Or Efficacy Concerns. (See below))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01496430
First received: December 18, 2011
Last updated: April 20, 2015
Last verified: April 2015
Results First Received: May 14, 2014  
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
Conditions: Hypertension
Diabetes
Interventions: Drug: Placebo
Drug: Azilsartan medoxomil

  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 41 investigative sites in the United States from 09 January 2012 to 30 May 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of stage 1 essential hypertension and type 2 diabetes mellitus uncontrolled on metformin were enrolled equally in 1 of 3 treatment groups, once a day placebo, 40 mg or 80 mg TAK-491.

Reporting Groups
  Description
Placebo QD Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.
Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.
Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.

Participant Flow:   Overall Study
    Placebo QD     Azilsartan Medoxomil 40 mg QD     Azilsartan Medoxomil 80 mg QD  
STARTED     35     35     35  
COMPLETED     29     30     25  
NOT COMPLETED     6     5     10  
Adverse Event                 0                 0                 1  
Major Protocol Deviation                 0                 0                 1  
Lost to Follow-up                 2                 3                 1  
Voluntary Withdrawal                 2                 1                 6  
Principal Investigator Discretion                 0                 1                 1  
Other                 2                 0                 0  



  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.
Randomized Set includes all enrolled participants who were randomized via the Interactive Voice/Web Response System.

Reporting Groups
  Description
Placebo QD Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.
Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.
Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo QD     Azilsartan Medoxomil 40 mg QD     Azilsartan Medoxomil 80 mg QD     Total  
Number of Participants  
[units: participants]
  35     35     35     105  
Age  
[units: years]
Mean (Standard Deviation)
  57.1  (8.66)     54.7  (7.63)     55.8  (7.37)     55.9  (7.89)  
Age, Customized  
[units: participants]
       
<45 years     3     3     2     8  
Between 45 and 64 years     25     29     30     84  
≥65 years     7     3     3     13  
Gender  
[units: participants]
       
Female     14     10     18     42  
Male     21     25     17     63  
Race/Ethnicity, Customized  
[units: participants]
       
Hispanic or Latino     11     15     14     40  
Non-Hispanic or Latino     24     20     21     65  
Race/Ethnicity, Customized  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     4     5     2     11  
Black or African American     6     6     7     19  
Native Hawaiian or Other Pacific Islander     0     1     0     1  
White     25     23     26     74  
Region of Enrollment  
[units: participants]
       
United States     35     35     35     105  
Height  
[units: cm]
Mean (Standard Deviation)
  169.4  (9.81)     169.8  (9.41)     167.0  (12.30)     168.8  (10.56)  
Weight  
[units: kg]
Mean (Standard Deviation)
  93.41  (19.165)     94.56  (20.084)     92.33  (24.027)     93.43  (21.012)  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean (Standard Deviation)
  32.50  (5.977)     32.58  (5.475)     32.94  (7.339)     32.67  (6.255)  
Smoking Classification  
[units: participants]
       
Never smoked     17     23     21     61  
Current smoker     11     2     3     16  
Ex-smoker     7     10     11     28  
Baseline Glycosylated Hemoglobin (HbA1c)  
[units: participants]
       
≤8.5%     24     24     20     68  
>8.5%     11     11     15     37  
Estimated Glomerular Filtration Rate (eGFR)  
[units: ml/min/1.73┬ám^2]
Mean (Standard Deviation)
  87.86  (18.068)     89.31  (15.631)     89.72  (18.379)     88.96  (17.253)  
Estimated Glomerular Filtration Rate (eGFR) Categories  
[units: participants]
       
30 - <60 mL/min/1.73 m^2     0     0     2     2  
60 - <90 mL/min/1.73 m^2     21     19     17     57  
≥90 mL/min/1.73 m^2     14     16     16     46  
Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category  
[units: participants]
       
SBP <140 mm Hg     16     6     13     35  
140 ≤SBP <160 mm Hg     19     23     16     58  
160 ≤SBP <180 mm Hg     0     6     5     11  
SBP ≥ 180 mm Hg     0     0     1     1  
Baseline Diastolic Blood Pressure (DBP) Hypertension Severity Category  
[units: participants]
       
DBP < 90 mm Hg     25     18     25     68  
DBP ≥ 90 mm Hg     10     17     10     37  
Antihypertension Medication Within 28 Days  
[units: participants]
       
Yes     32     27     30     89  
No     3     8     5     16  
Washout Required  
[units: participants]
       
21-Day Washout     27     24     25     76  
4 Week Washout     3     2     4     9  
Missing     5     9     6     20  
Female Reproductive Status  
[units: participants]
       
Postmenopausal     4     5     9     18  
Surgically Sterile     6     3     8     17  
Female of Childbearing Potential     4     2     1     7  
N/A (participant is male)     21     25     17     63  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure   [ Time Frame: Baseline and Week 8 ]

2.  Secondary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c)   [ Time Frame: Baseline and Week 24 ]

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

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

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

6.  Secondary:   Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

7.  Secondary:   Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

8.  Secondary:   Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

9.  Secondary:   Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

10.  Secondary:   Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

11.  Secondary:   Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

12.  Secondary:   Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

13.  Secondary:   Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring   [ Time Frame: Baseline and Week 8 ]

14.  Secondary:   Percentage of Participants Requiring Rescue Glycemic Therapy   [ Time Frame: 24 Weeks ]

15.  Secondary:   Time to First Glycemic Rescue   [ Time Frame: 24 Weeks ]

16.  Secondary:   Change From Baseline in HbA1c   [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 12, 16 and 20 ]

17.  Secondary:   Change From Baseline in Fasting Plasma Glucose   [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24 ]

18.  Secondary:   Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT)   [ Time Frame: Baseline and Weeks 6 and 24 ]

19.  Secondary:   Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT   [ Time Frame: Baseline and Weeks 6 and 24 ]

20.  Secondary:   Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT   [ Time Frame: Baseline and Weeks 6 and 24 ]

21.  Secondary:   Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT   [ Time Frame: Baseline and Weeks 6 and 24 ]

22.  Secondary:   Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT   [ Time Frame: Baseline and Weeks 6 and 24 ]

23.  Secondary:   Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT   [ Time Frame: Baseline and Weeks 6 and 24 ]


  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
Because of low enrollment in the study, the sample sizes in the results data do not allow for significant interpretation of the results.


  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: Medical Director; Clinical Science
Organization: Takeda
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


No publications provided


Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01496430     History of Changes
Other Study ID Numbers: TAK-491_304, U1111-1125-1197
Study First Received: December 18, 2011
Results First Received: May 14, 2014
Last Updated: April 20, 2015
Health Authority: United States: Food and Drug Administration