Safety and Efficacy of Azilsartan Medoxomil in Participants With Mild to Moderate Hypertension

This study has been completed.

Sponsor:

Information provided by:

Takeda Global Research & Development Center, Inc.

ClinicalTrials.gov Identifier:

NCT00362115

First received: August 7, 2006

Last updated: March 24, 2011

Last verified: March 2011

History of Changes

Results First Received: March 24, 2011

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:	Hypertension
Interventions:	Drug: Azilsartan Medoxomil Drug: Olmesartan Drug: Placebo

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 enrolled at 76 investigative sites in Argentina, Mexico, Peru and the United States from 16 May 2006 to 07 December 2006.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with mild to moderate uncomplicated essential hypertension were enrolled in one of seven, once-daily (QD) treatment groups.

Reporting Groups

	Description
Azilsartan Medoxomil 5 mg QD	Azilsartan medoxomil 5 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 10 mg QD	Azilsartan medoxomil 10 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 20 mg QD	Azilsartan medoxomil 20 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 40 mg QD	Azilsartan medoxomil 40 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 80 mg QD	Azilsartan medoxomil 80 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Olmesartan 20 mg QD	Olmesartan 20 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Placebo QD	Matching placebo tablets, orally, once daily for up to 8 weeks.

Participant Flow: Overall Study

	Azilsartan Medoxomil 5 mg QD	Azilsartan Medoxomil 10 mg QD	Azilsartan Medoxomil 20 mg QD	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Olmesartan 20 mg QD	Placebo QD
STARTED	65	65 ^[1]	64	63 ^[1]	64	64 ^[1]	64 ^[1]
COMPLETED	63	59	57	59	57	57	52
NOT COMPLETED	2	6	7	4	7	7	12
Adverse Event	0	1	1	1	2	2	1
Protocol Violation	0	0	0	0	0	1	0
Lost to Follow-up	0	1	0	0	2	0	1
Withdrawal by Subject	1	3	1	0	1	3	4
Lack of Efficacy	1	0	5	2	2	0	3
Physician Decision	0	0	0	0	0	0	3
Other	0	1	0	1	0	1	0

[1]	1 participant failed to receive double-blind medication.

Baseline Characteristics

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Reporting Groups

	Description
Azilsartan Medoxomil 5 mg QD	Azilsartan medoxomil 5 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 10 mg QD	Azilsartan medoxomil 10 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 20 mg QD	Azilsartan medoxomil 20 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 40 mg QD	Azilsartan medoxomil 40 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 80 mg QD	Azilsartan medoxomil 80 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Olmesartan 20 mg QD	Olmesartan 20 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Placebo QD	Matching placebo tablets, orally, once daily for up to 8 weeks.
Total	Total of all reporting groups

Baseline Measures

	Azilsartan Medoxomil 5 mg QD	Azilsartan Medoxomil 10 mg QD	Azilsartan Medoxomil 20 mg QD	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Olmesartan 20 mg QD	Placebo QD	Total
Number of Participants [units: participants]	65	63	64	62	64	63	61	442
Age [units: participants]
<45 years	12	5	10	9	12	10	11	69
Between 45 and 64 years	45	52	46	43	41	46	36	309
≥65 years	8	6	8	10	11	7	14	64
Gender [units: participants]
Female	29	32	30	33	28	34	32	218
Male	36	31	34	29	36	29	29	224

Outcome Measures

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1. Primary:

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

Show Outcome Measure 1

2. Secondary:

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

Show Outcome Measure 2

3. Secondary:

Change From Baseline in Standing Clinic Systolic Blood Pressure. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 3

4. Secondary:

Change From Baseline in Standing Clinic Diastolic Blood Pressure. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 4

5. Secondary:

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

Show Outcome Measure 5

6. Secondary:

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

Show Outcome Measure 6

7. Secondary:

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

Show Outcome Measure 7

8. Secondary:

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

Show Outcome Measure 8

9. Secondary:

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

Show Outcome Measure 9

10. Secondary:

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

Show Outcome Measure 10

11. Secondary:

Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8 ]

Hide Outcome Measure 11

Measure Type	Secondary
Measure Title	Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Measure Description	The change in trough mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame	Baseline and Week 8
Safety Issue	No

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.
Full Analysis Set.

Reporting Groups

	Description
Azilsartan Medoxomil 5 mg QD	Azilsartan medoxomil 5 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 10 mg QD	Azilsartan medoxomil 10 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 20 mg QD	Azilsartan medoxomil 20 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 40 mg QD	Azilsartan medoxomil 40 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Azilsartan Medoxomil 80 mg QD	Azilsartan medoxomil 80 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Olmesartan 20 mg QD	Olmesartan 20 mg and comparator matching placebo tablets, orally, once daily for up to 8 weeks.
Placebo QD	Matching placebo tablets, orally, once daily for up to 8 weeks.

Measured Values

	Azilsartan Medoxomil 5 mg QD	Azilsartan Medoxomil 10 mg QD	Azilsartan Medoxomil 20 mg QD	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Olmesartan 20 mg QD	Placebo QD
Number of Participants Analyzed [units: participants]	53	43	45	38	44	48	39
Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [units: mmHg] Least Squares Mean ± Standard Error	-10.9 ± 1.78	-14.9 ± 1.98	-12.0 ± 1.93	-18.8 ± 2.10	-13.9 ± 1.95	-13.8 ± 1.87	-1.5 ± 2.08

Statistical Analysis 1 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 5 mg QD vs. Placebo QD
Method ^[2]	ANCOVA
P Value ^[3]	0.0007
Mean Difference (Final Values) ^[4]	-9.4
95% Confidence Interval	( -14.74 to -3.97 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 10 mg QD vs. Placebo QD
Method ^[2]	ANCOVA
P Value ^[3]	< 0.0001
Mean Difference (Final Values) ^[4]	-13.4
95% Confidence Interval	( -19.02 to -7.73 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 20 mg QD vs. Placebo QD
Method ^[2]	ANCOVA
P Value ^[3]	0.0003
Mean Difference (Final Values) ^[4]	-10.4
95% Confidence Interval	( -16.00 to -4.83 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 40 mg QD vs. Placebo QD
Method ^[2]	ANCOVA
P Value ^[3]	< 0.0001
Mean Difference (Final Values) ^[4]	-17.3
95% Confidence Interval	( -23.11 to -11.47 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 80 mg QD vs. Placebo QD
Method ^[2]	ANCOVA
P Value ^[3]	< 0.0001
Mean Difference (Final Values) ^[4]	-12.4
95% Confidence Interval	( -18.01 to -6.78 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 5 mg QD vs. Olmesartan 20 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.2594
Mean Difference (Final Values) ^[4]	2.9
95% Confidence Interval	( -2.17 to 8.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 10 mg QD vs. Olmesartan 20 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.6859
Mean Difference (Final Values) ^[4]	-1.1
95% Confidence Interval	( -6.46 to 4.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 20 mg QD vs. Olmesartan 20 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.4898
Mean Difference (Final Values) ^[4]	1.9
95% Confidence Interval	( -3.43 to 7.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 40 mg QD vs. Olmesartan 20 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.0760
Mean Difference (Final Values) ^[4]	-5.0
95% Confidence Interval	( -10.55 to 0.53 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

Groups ^[1]	Azilsartan Medoxomil 80 mg QD vs. Olmesartan 20 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.9647
Mean Difference (Final Values) ^[4]	-0.1
95% Confidence Interval	( -5.44 to 5.21 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value from analysis of covariance with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
[4]	Other relevant estimation information:
	No text entered.

12. Secondary:

Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 12

13. Secondary:

Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 13

14. Secondary:

Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 14

15. Secondary:

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

Show Outcome Measure 15

16. Secondary:

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

Show Outcome Measure 16

17. Secondary:

Change From Baseline in the 24-36-Hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 17

18. Secondary:

Change From Baseline in the 24-36-Hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in the 34-36-Hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8 ]

Show Outcome Measure 19

20. Secondary:

Change From Baseline in the 34-36-Hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 8. ]

Show Outcome Measure 20

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.

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.

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:	Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00362115 History of Changes
Other Study ID Numbers:	01-05-TL-491-005, U1111-1113-8783
Study First Received:	August 7, 2006
Results First Received:	March 24, 2011
Last Updated:	March 24, 2011
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Peru: General Directorate of Pharmaceuticals, Devices, and Drugs Chile: Instituto de Salud Publica de Chile Mexico: Ministry of Health

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