Trial Outcomes & Findings for Safety and Efficacy Study of a Triple Combination Therapy in Subjects With Hypertension (NCT NCT00649389)

NCT ID: NCT00649389

Last Updated: 2019-01-09

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2500 participants

Primary outcome timeframe

baseline to 12 weeks

Results posted on

2019-01-09

Participant Flow

First subject first visit 12 May 2008. Last subject last follow-up 27 Feb 2009. 317 sites in USA and Puerto Rico. Planned: 2400 subjects (600 per treatment arm). Enrolled: 6724 subjects. Randomized: 2492 subjects.

Duration of the study was 57 weeks with 52 weeks of treatment. This included 3-week stabilization/washout (Period I), 12-week double blind treatment (Period II), 40 week open label treatment (Period III), and 2-week post treatment follow-up (Period IV).

Participant milestones

Participant milestones
Measure	OM40/AML10 Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Overall Study STARTED	628	637	600	627
Overall Study COMPLETED	557	531	512	516
Overall Study NOT COMPLETED	71	106	88	111

Reasons for withdrawal

Reasons for withdrawal
Measure	OM40/AML10 Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Overall Study Adverse Event	22	46	38	48
Overall Study Lost to Follow-up	15	17	21	26
Overall Study Protocol Violation	11	13	9	8
Overall Study Withdrawal by Subject	20	21	19	23
Overall Study Other	3	9	1	6

Baseline Characteristics

Safety and Efficacy Study of a Triple Combination Therapy in Subjects With Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OM40/AML10 n=628 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 n=637 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 n=600 Participants Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 n=627 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.	Total n=2492 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	508 Participants n=5 Participants	505 Participants n=7 Participants	504 Participants n=5 Participants	504 Participants n=4 Participants	2021 Participants n=21 Participants
Age, Categorical >=65 years	120 Participants n=5 Participants	132 Participants n=7 Participants	96 Participants n=5 Participants	123 Participants n=4 Participants	471 Participants n=21 Participants
Age, Continuous	55.1 years STANDARD_DEVIATION 10.93 • n=5 Participants	55.9 years STANDARD_DEVIATION 10.78 • n=7 Participants	54.6 years STANDARD_DEVIATION 10.82 • n=5 Participants	54.7 years STANDARD_DEVIATION 11.22 • n=4 Participants	55.1 years STANDARD_DEVIATION 10.94 • n=21 Participants
Sex: Female, Male Female	303 Participants n=5 Participants	298 Participants n=7 Participants	266 Participants n=5 Participants	307 Participants n=4 Participants	1174 Participants n=21 Participants
Sex: Female, Male Male	325 Participants n=5 Participants	339 Participants n=7 Participants	334 Participants n=5 Participants	320 Participants n=4 Participants	1318 Participants n=21 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Race/Ethnicity, Customized Asian	13 Participants n=5 Participants	10 Participants n=7 Participants	7 Participants n=5 Participants	19 Participants n=4 Participants	49 Participants n=21 Participants
Race/Ethnicity, Customized Hawaiian/Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Black/African American	181 Participants n=5 Participants	200 Participants n=7 Participants	192 Participants n=5 Participants	184 Participants n=4 Participants	757 Participants n=21 Participants
Race/Ethnicity, Customized White	431 Participants n=5 Participants	421 Participants n=7 Participants	391 Participants n=5 Participants	415 Participants n=4 Participants	1658 Participants n=21 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	15 Participants n=21 Participants
Diabetes Status Diabetic	100 Participants n=5 Participants	99 Participants n=7 Participants	92 Participants n=5 Participants	96 Participants n=4 Participants	387 Participants n=21 Participants
Diabetes Status Not diabetic	528 Participants n=5 Participants	538 Participants n=7 Participants	508 Participants n=5 Participants	531 Participants n=4 Participants	2105 Participants n=21 Participants
Weight	95.9 kg STANDARD_DEVIATION 22.65 • n=5 Participants	96.1 kg STANDARD_DEVIATION 22.55 • n=7 Participants	96.1 kg STANDARD_DEVIATION 23.41 • n=5 Participants	96.0 kg STANDARD_DEVIATION 23.24 • n=4 Participants	96.0 kg STANDARD_DEVIATION 22.94 • n=21 Participants
Body Mass Index Less than 30 kg/m2	229 Participants n=5 Participants	238 Participants n=7 Participants	230 Participants n=5 Participants	240 Participants n=4 Participants	937 Participants n=21 Participants
Body Mass Index Greater than or equal to 30 kg/m2	399 Participants n=5 Participants	399 Participants n=7 Participants	370 Participants n=5 Participants	387 Participants n=4 Participants	1555 Participants n=21 Participants
Duration of hypertension	10.12 years STANDARD_DEVIATION 9.865 • n=5 Participants	10.34 years STANDARD_DEVIATION 9.826 • n=7 Participants	9.73 years STANDARD_DEVIATION 8.983 • n=5 Participants	9.54 years STANDARD_DEVIATION 9.558 • n=4 Participants	9.94 years STANDARD_DEVIATION 9.571 • n=21 Participants

PRIMARY outcome

Timeframe: baseline to 12 weeks

Population: The full analysis set consists of subjects who received at least 1 dose of study medication and had a baseline and at least one post-dose assessment of SeDBP

Outcome measures

Outcome measures
Measure	OM40/AML10 n=624 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 n=627 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 n=593 Participants Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 n=614 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Change From Baseline to Week 12 in Seated Diastolic Blood Pressure (SeDBP).	-17.8 mm Hg Standard Deviation 9.47	-16.5 mm Hg Standard Deviation 10.84	-14.8 mm Hg Standard Deviation 8.78	-21.5 mm Hg Standard Deviation 10.25

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: The full analysis set consists of subjects who received at least 1 dose of study medication and had a baseline and at least one post-dose assessment of seated diastolic blood pressure

Outcome measures

Outcome measures
Measure	OM40/AML10 n=624 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 n=627 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 n=593 Participants Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 n=614 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Percentage of Subjects Who Reached Blood Pressure Goal (<140/90 mmHg; <130/80 mmHg for Subjects With Diabetes, Chronic Renal Disease, or Chronic Cardiovascular Disease)by 12 Weeks	46.0 Percentage of subjects	46.6 Percentage of subjects	34.9 Percentage of subjects	64.3 Percentage of subjects

SECONDARY outcome

Timeframe: Baseline to 12 weeks or early termination

Population: The ABPM Analysis Set included 440 subjects who provided consent to participate in the ABPM sub-study and who were to provide ABPM measurements prior to and after randomization. Those analyzed is the number who had values at both baseline and 12 weeks or early termination

Outcome measures

Outcome measures
Measure	OM40/AML10 n=96 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 n=101 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 n=83 Participants Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 n=100 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Change in Mean 24-hour Ambulatory Blood Pressure From Baseline to Week 12 or Early Termination Diastolic blood pressure	-13.9 mm Hg Standard Deviation 8.09	-14.5 mm Hg Standard Deviation 8.73	-10.7 mm Hg Standard Deviation 7.46	-18.0 mm Hg Standard Deviation 8.11
Change in Mean 24-hour Ambulatory Blood Pressure From Baseline to Week 12 or Early Termination Systolic blood pressure	-23.5 mm Hg Standard Deviation 11.80	-23.9 mm Hg Standard Deviation 13.10	-18.5 mm Hg Standard Deviation 10.67	-30.3 mm Hg Standard Deviation 13.85

SECONDARY outcome

Timeframe: Baseline to week 12

Outcome measures

Outcome measures
Measure	OM40/AML10 n=624 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 n=627 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 n=593 Participants Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 n=614 Participants Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Change in Seated Systolic Blood Pressure From Baseline to Week 12	-31.1 mm Hg Standard Deviation 15.44	-31.2 mm Hg Standard Deviation 18.58	-28.9 mm Hg Standard Deviation 15.12	-38.1 mm Hg Standard Deviation 17.40

Adverse Events

OM40/AML10

Serious events: 9 serious events

Other events: 210 other events

Deaths: 0 deaths

OM40/HCTZ25

Serious events: 7 serious events

Other events: 210 other events

Deaths: 0 deaths

AML10/HCTZ25

Serious events: 9 serious events

Other events: 212 other events

Deaths: 0 deaths

OM40/AML10/HCTZ25

Serious events: 10 serious events

Other events: 237 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	OM40/AML10 n=596 participants at risk Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg tablets once daily.	OM40/HCTZ25 n=580 participants at risk Double blind treatment olmesartan medoxomil (OM) 40 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	AML10/HCTZ25 n=552 participants at risk Double blind treatment Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg tablets once daily.	OM40/AML10/HCTZ25 n=574 participants at risk Double blind treatment olmesartan medoxomil (OM) 40 mg, Amlodipine (AML) 10 mg, Hydrochlorothiazide (HCTZ) 25 mg, tablets once daily.
Nervous system disorders dizziness	4.9% 29/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	10.0% 58/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.1% 17/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	9.9% 57/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
Nervous system disorders headache	7.0% 42/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	6.6% 38/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	6.0% 33/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	6.4% 37/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
Infections and infestations upper respiratory tract infection	4.4% 26/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.1% 18/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	2.5% 14/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	2.8% 16/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
Infections and infestations nasopharyngitis	1.8% 11/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.4% 20/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	2.9% 16/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.5% 20/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
General disorders edema peripheral	7.0% 42/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	1.0% 6/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	8.3% 46/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	7.7% 44/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
General disorders fatigue	5.7% 34/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	5.3% 31/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	6.5% 36/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	4.2% 24/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
Musculoskeletal and connective tissue disorders muscle spasms	2.0% 12/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	2.4% 14/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	2.4% 13/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.1% 18/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
Gastrointestinal disorders nausea	2.0% 12/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.8% 22/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	2.2% 12/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	3.0% 17/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.
Metabolism and nutrition disorders hypokalemia	0.34% 2/596 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	0.52% 3/580 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	4.5% 25/552 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.	0.70% 4/574 • 12 weeks Safety was assessed at all study visits. Variables included adverse events, clinical laboratory tests, vital signs, ECGs, and physical examinations. The assessment of causality was based on the investigator's judgment.

Additional Information

Howard Kessler

Daiichi Sankyo

Phone: 732-590-5032

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Study site may not publish results of study until after coordinated multicenter publication has been submitted for publication or one year after study has ended, whichever occurs first. Therefore, study site will have the opportunity to publish results of study, provided that Daiichi Sankyo has had the opportunity to review and comment on study site's proposed publication prior to being submitted for publication with advice of company patent council and in accord with subject protection needs.
Publication restrictions are in place

Restriction type: OTHER