Hydrochlorothiazide as add-on to Olmesartan/Amlodipine in Hypertension - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Treatment
Condition:	Essential Hypertension
Interventions:	Drug: Olmesartan medoxomil 40 mg - Amlodipine 10 mg Drug: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg Drug: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First participant visit was 29 April 2009. The last participant follow up was 07 September 2010

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The number of subjects entering Period 2 was only 808 because 1278 did not meet the entry criteria.

Reporting Groups

	Description
Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg	The participants in this arm received Olmesartan(OLM) 40 mg-Amlodipine(AML) 10 mg oral tablets, once a day, for the 8-week, single-blind, run-in Period 1. Then in Period 2, participants would be randomized to this same combination or have hydrochlorothiazide oral tablets (12.5 or 25 mg) added for an additional 8 weeks. All medication is given once a day.
OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5	Participants could start receiving OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 oral tablets given once daily in randomized, double-blind, 8-week Period 2. This combination was continued into single-blind, 8-week Period 3 for all participants entering Period 3.
OLM 40-AML 10-HCTZ 25	Participants could start receiving OLM 40-AML 10-HCTZ 25 oral tablets, given once daily, in randomized, double-blind, 8- week Period 2.
OLM 40-AML 10-HCTZ 12.5 (Responders)	Participants who meet their blood pressure goals (responded) in Period 3 and continued into 8-week, double-blind Period 4 continued to receive OLM 40-AML 10-HCTZ 12.5 oral tablets given once daily.
OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 (Non-responders)	Participants finishing Period 3, but, who did not meet their blood pressure goals (non-responders) could receive OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 oral tablets, given once daily, in double-blind, randomized, Period 4.
OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 25 (Non-responders)	Participants finishing Period 3, but, who did not meet their blood pressure goals (non-responders) could receive OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 25 oral tablets, given once daily, in double-blind, randomized, Period 4

Participant Flow for 4 periods

Period 1: 1-Single-blind, Run-in, Single-Treatment

	Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5	OLM 40-AML 10-HCTZ 25	OLM 40-AML 10-HCTZ 12.5 (Responders)	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 (Non-responders)	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 25 (Non-responders)
STARTED	2204	0	0	0	0	0
COMPLETED	2086	0	0	0	0	0
NOT COMPLETED	118	0	0	0	0	0
Adverse Event	49	0	0	0	0	0
Withdrawal by Subject	30	0	0	0	0	0
Protocol Violation	22	0	0	0	0	0
Other Reason	13	0	0	0	0	0
Lost to Follow-up	4	0	0	0	0	0

Period 2: 2-Randomized Double-blind 3 Treatments

	Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5	OLM 40-AML 10-HCTZ 25
STARTED	269 ^[1]	269	270
COMPLETED	260	263	262
NOT COMPLETED	9	6	8
Adverse Event	4	2	3
Withdrawal by Subject	1	2	1
Lost to Follow-up	1	0	2
Unknown	2	1	0
Protocol Violation	1	1	2

[1]	Only 808 began Period 2 because the others finishing Period 1 did not meet the entry criteria.

Period 3: 3-Single-blind, Single Treatment

	Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5	OLM 40-AML 10-HCTZ 25	OLM 40-AML 10-HCTZ 12.5 (Responders)	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 (Non-responders)	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 25 (Non-responders)
STARTED	0	782 ^[1]	0	0	0	0
COMPLETED	0	767	0	0	0	0
NOT COMPLETED	0	15	0	0	0	0
Adverse Event	0	5	0	0	0	0
Protocol Violation	0	5	0	0	0	0
Withdrawal by Subject	0	4	0	0	0	0
Lost to Follow-up	0	1	0	0	0	0

[1]	Number starting is < total completing previous arm since 3 subjects did not receive at least 1 dose.

Period 4: 4-Randomized Double-blind 2 Treatments

	OLM 40-AML 10-HCTZ 12.5 (Responders)	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 (Non-responders)	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 25 (Non-responders)
STARTED	467 ^[1]	97 ^[2]	197
COMPLETED	458	95	196
NOT COMPLETED	9	2	1
Adverse Event	3	1	1
Withdrawal by Subject	3	1	0
Protocol Violation	3	0	0

[1]	Period 3 responders were continued on OLM 40-AML 10-HCTZ 12.5
[2]	Period 3 non-responders were randomized to OLM 40-AML 10-HCTZ 12.5 or 25 in a 2:1 ratio

Baseline Characteristics

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Reporting Groups

	Description
Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg	The participants in this arm received these 2 drugs for the 8-week, single-blind, run-in Period 1. Participants could then randomized to this same combination for an additional 8 weeks in the double-blind, Period 2.
OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5	Participants could start receiving this combination in randomized, double-blind, 8- week Period 2. This combination was continued into single-blind, 8-week Period 3 for all participants entering Period 3
OLM 40-AML 10-HCTZ 25	Participants could start receiving this combination in randomized, double-blind, 8- week Period 2.

Baseline Measures

	Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg	OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5	OLM 40-AML 10-HCTZ 25	Total
Number of Participants [units: participants]	269	269	270	808
Age [units: years] Mean ± Standard Deviation	55.9 ± 10.56	56.5 ± 10.25	54.9 ± 10.44	55.8 ± 10.42
Gender [units: participants]
Female	119	104	116	339
Male	150	165	154	469
Race (NIH/OMB) [units: Participant]
American Indian or Alaska Native	0	0	0	0
Asian	0	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	269	269	269	807
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0
Weight [units: kg] Mean ± Standard Deviation	87.8 ± 18.14	88.2 ± 16.03	88.5 ± 16.28	88.2 ± 16.83
Height [units: cm] Mean ± Standard Deviation	169.9 ± 9.74	170.5 ± 9.11	170.4 ± 8.98	170.3 ± 9.27
Body Mass Index [units: kg/m^2] Mean ± Standard Deviation	30.27 ± 4.90	30.30 ± 4.65	30.44 ± 4.87	30.34 ± 4.80
Obesity ^[1] [units: Participants]
Body Mass Index < 30 kg/m^2	138	142	133	413
Body Mass Index >= 30 kg/m^2	131	125	137	393

[1]	Number of participants whose Body Mass Index (BMI) is <30 kg/m^2 or whose number is >=30 kg/m^2. Only 806 participants had their BMI measured.

Outcome Measures

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1. Primary:

Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg [ Time Frame: baseline (8 weeks) to 16 weeks ]

Show Outcome Measure 1

2. Secondary:

Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg [ Time Frame: baseline (8 weeks) to week 16 ]

Show Outcome Measure 2

3. Secondary:

Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16. [ Time Frame: baseline (week 8) to week 16 ]

Show Outcome Measure 3

4. Secondary:

Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM). [ Time Frame: Baseline (8 weeks) to 16 weeks ]

Show Outcome Measure 4

5. Secondary:

Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. [ Time Frame: Baseline (8 weeks) to 16 weeks ]

Show Outcome Measure 5

6. Secondary:

In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. [ Time Frame: week 24 to week 32 ]

Show Outcome Measure 6

7. Secondary:

In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. [ Time Frame: week 24 to week 32 ]

Show Outcome Measure 7

8. Secondary:

In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. [ Time Frame: week 24 to week 32 ]

Show Outcome Measure 8

9. Secondary:

In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. [ Time Frame: Week 16 to week 32 ]

Show Outcome Measure 9

10. Secondary:

In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. [ Time Frame: Week 16 to week 32 ]

Show Outcome Measure 10

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: A site may not publish results until after a multi-center publication has been submitted for publication or until one year after the study has ended, whichever occurs first. Then, the site will have the opportunity to publish the results, provided that Daiichi Sankyo Europe has had the opportunity to review and comment on the site’s proposed publication prior to its being submitted for publication with the advice of company patent council and in accord with needs for subject protection.

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
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Results Point of Contact:

Name/Title: Bettina Ammentorp
Organization: Daiichi Sankyo Europe GmbH
phone: 0049 89 7808 0 ext 585
e-mail: bettina.ammentorp@daiichi-sankyo.eu

No publications provided

Responsible Party:	Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:	NCT00902538 History of Changes
Other Study ID Numbers:	CS8635-A-E303
Study First Received:	May 13, 2009
Results First Received:	September 6, 2011
Last Updated:	February 20, 2012
Health Authority:	Austria: Federal Office for Safety in Health Care France: Afssaps - French Health Products Safety Agency Germany: Federal Institute for Drugs and Medical Devices Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)