Trial Outcomes & Findings for Olmesartan Comparison to Losartan in Hypertensive Subjects (NCT NCT00949884)

Last Updated: 2011-03-09

Results Overview

The change from baseline in trough SDBP at Week 8 as measured by the Omron monitor. Morning doses of study medication were taken after the exam on study visit days, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

941 participants

Primary outcome timeframe

Day 0, Week 8

Results posted on

2011-03-09

Participant Flow

Participants were enrolled at 119 out-patient centers throughout the U.S.: 1976 patients were screened, 1632 were enrolled, and 941 randomized.

Prior to group assignment was a 2-9 day screening period and a 3-4 week single-blind (participant was blinded) placebo run-in period. Participants were randomized in an 8:1:9 ratio to treatment arms as listed.

Participant milestones

Participant milestones
Measure	Olmesartan Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Placebo Followed by Olmesartan Placebo capsule of olmesartan once daily for 2 weeks, followed by olmesartan 20 mg once daily for two weeks, followed by olmesartan 40 mg for 4 weeks	Losartan Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Overall Study STARTED	420	52	469
Overall Study COMPLETED	370	37	411
Overall Study NOT COMPLETED	50	15	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Olmesartan Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Placebo Followed by Olmesartan Placebo capsule of olmesartan once daily for 2 weeks, followed by olmesartan 20 mg once daily for two weeks, followed by olmesartan 40 mg for 4 weeks	Losartan Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Overall Study Adverse Event	14	3	12
Overall Study Did not meet inclusion/exclusion	2	1	3
Overall Study Lost to Follow-up	7	5	5
Overall Study Physician Decision	5	0	6
Overall Study Treatment non-compliance	5	0	8
Overall Study Withdrawal by Subject	13	4	16
Overall Study Lack of Efficacy	4	2	7
Overall Study Study terminated by sponsor	0	0	1

Baseline Characteristics

Olmesartan Comparison to Losartan in Hypertensive Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olmesartan n=420 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Placebo Followed by Olmesartan n=52 Participants Placebo capsule of olmesartan once daily for 2 weeks, followed by olmesartan 20 mg once daily for two weeks, followed by olmesartan 40 mg for 4 weeks	Losartan n=469 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks	Total n=941 Participants Total of all reporting groups
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants	2 Participants n=7 Participants	26 Participants n=5 Participants	53 Participants n=4 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	385 Participants n=5 Participants	51 Participants n=7 Participants	423 Participants n=5 Participants	859 Participants n=4 Participants
Age, Categorical >=65 years	35 Participants n=5 Participants	1 Participants n=7 Participants	46 Participants n=5 Participants	82 Participants n=4 Participants
Age Continuous	52.0 years STANDARD_DEVIATION 9.84 • n=5 Participants	49.9 years STANDARD_DEVIATION 8.67 • n=7 Participants	52.1 years STANDARD_DEVIATION 9.76 • n=5 Participants	51.9 years STANDARD_DEVIATION 9.74 • n=4 Participants
Sex: Female, Male Female	190 Participants n=5 Participants	27 Participants n=7 Participants	211 Participants n=5 Participants	428 Participants n=4 Participants
Sex: Female, Male Male	230 Participants n=5 Participants	25 Participants n=7 Participants	258 Participants n=5 Participants	513 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	52 Participants n=5 Participants	7 Participants n=7 Participants	61 Participants n=5 Participants	120 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	368 Participants n=5 Participants	45 Participants n=7 Participants	408 Participants n=5 Participants	821 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	118 Participants n=5 Participants	16 Participants n=7 Participants	133 Participants n=5 Participants	267 Participants n=4 Participants
Race (NIH/OMB) White	273 Participants n=5 Participants	33 Participants n=7 Participants	304 Participants n=5 Participants	610 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Hypertension stage Stage I	120 participants n=5 Participants	23 participants n=7 Participants	134 participants n=5 Participants	277 participants n=4 Participants
Hypertension stage Stage II	300 participants n=5 Participants	29 participants n=7 Participants	335 participants n=5 Participants	664 participants n=4 Participants
Height	169.92 centimeter STANDARD_DEVIATION 9.635 • n=5 Participants	169.46 centimeter STANDARD_DEVIATION 9.652 • n=7 Participants	170.47 centimeter STANDARD_DEVIATION 9.906 • n=5 Participants	170.17 centimeter STANDARD_DEVIATION 9.767 • n=4 Participants
Weight	93.73 kilogram STANDARD_DEVIATION 19.627 • n=5 Participants	96.14 kilogram STANDARD_DEVIATION 22.611 • n=7 Participants	94.02 kilogram STANDARD_DEVIATION 21.647 • n=5 Participants	94.01 kilogram STANDARD_DEVIATION 20.810 • n=4 Participants
Body Mass Index	32.41 kilogram/meter^2 STANDARD_DEVIATION 6.089 • n=5 Participants	33.62 kilogram/meter^2 STANDARD_DEVIATION 8.103 • n=7 Participants	32.28 kilogram/meter^2 STANDARD_DEVIATION 6.619 • n=5 Participants	32.41 kilogram/meter^2 STANDARD_DEVIATION 6.480 • n=4 Participants
Systolic Blood Pressure	158.3 mmHg STANDARD_DEVIATION 10.41 • n=5 Participants	157.9 mmHg STANDARD_DEVIATION 10.05 • n=7 Participants	158.3 mmHg STANDARD_DEVIATION 10.24 • n=5 Participants	158.3 mmHg STANDARD_DEVIATION 10.29 • n=4 Participants
Diastolic Blood Pressure	101.1 mmHg STANDARD_DEVIATION 4.07 • n=5 Participants	100.8 mmHg STANDARD_DEVIATION 3.79 • n=7 Participants	101.3 mmHg STANDARD_DEVIATION 4.14 • n=5 Participants	101.2 mmHg STANDARD_DEVIATION 4.09 • n=4 Participants
Pulse Rate	78.8 beats per minute STANDARD_DEVIATION 11.41 • n=5 Participants	81.9 beats per minute STANDARD_DEVIATION 9.88 • n=7 Participants	78.5 beats per minute STANDARD_DEVIATION 10.59 • n=5 Participants	78.9 beats per minute STANDARD_DEVIATION 10.94 • n=4 Participants

PRIMARY outcome

Timeframe: Day 0, Week 8

Population: The Efficacy Population included participants who received at least 1 dose of double-blind randomized study medication and had a baseline and at least 1 post-baseline blood pressure measurement. Last observation carried forward.

Outcome measures

Outcome measures
Measure	Olmesartan n=384 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=424 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=426 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline to Week 8 in Trough, Cuff, Seated Diastolic Blood Pressure (SDBP)	-9.8 mmHg Standard Error 0.50	-9.7 mmHg Standard Error 0.45	-7.1 mmHg Standard Error 0.45

SECONDARY outcome

Timeframe: Day 0, Week 4

The change from baseline in trough SSBP at Week 4 as measured by the Omron monitor. Morning doses of study medication were taken after the exam on study visit days, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Outcome measures

Outcome measures
Measure	Olmesartan n=417 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=461 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=461 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline to Week 4 in Trough, Cuff, Seated Systolic Blood Pressure (SSBP)	-12.3 mmHg Standard Error 0.67	-12.0 mmHg Standard Error 0.64	-8.5 mmHg Standard Error 0.64

SECONDARY outcome

Timeframe: Day 0, Week 8

The change from baseline in trough SSBP at Week 8 as measured by the Omron monitor. Morning doses of study medication were taken after the exam on study visit days, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Outcome measures

Outcome measures
Measure	Olmesartan n=384 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=424 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=426 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline to Week 8 in Trough, Cuff, Seated Systolic Blood Pressure (SSBP)	-13.6 mmHg Standard Error 0.75	-13.6 mmHg Standard Error 0.71	-9.7 mmHg Standard Error 0.71

SECONDARY outcome

Timeframe: Day 0, Week 4

The change from baseline in trough SDBP at Week 4 as measured by the Omron monitor. Morning doses of study medication were taken after the exam on study visit days, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Outcome measures

Outcome measures
Measure	Olmesartan n=417 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=461 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=461 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline to Week 4 in Trough, Cuff, Seated Diastolic Blood Pressure (SDBP)	-9.0 mmHg Standard Error 0.44	-8.8 mmHg Standard Error 0.42	-6.2 mmHg Standard Error 0.42

POST_HOC outcome

Timeframe: Week 8

Population: Ambulatory Blood Pressure Monitoring (ABPM) Population: All participants in the Efficacy Population that had both valid (technically successful) baseline and Week 8 ambulatory blood pressure monitor data. A technically successful ABPM had at least 23 hours of ABPM data.

Participants from pre-selected sites had 24-hour ambulatory blood pressure readings collected. Daytime readings were results collected between 8am and 4pm. Nighttime readings were results collected between 10pm and 6am.

Outcome measures

Outcome measures
Measure	Olmesartan n=98 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=106 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=110 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Percentage of Participants Achieving Ambulatory Blood Pressure Goal of < 135/85 mmHg at Week 8 Mean 24-hour	59.2 percentage of population	58.5 percentage of population	40.9 percentage of population
Percentage of Participants Achieving Ambulatory Blood Pressure Goal of < 135/85 mmHg at Week 8 Mean Daytime	32.7 percentage of population	32.1 percentage of population	21.8 percentage of population
Percentage of Participants Achieving Ambulatory Blood Pressure Goal of < 135/85 mmHg at Week 8 Mean Nighttime	76.5 percentage of population	77.4 percentage of population	66.4 percentage of population

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4, Week 8

The change from Week 4 in trough SDBP at Week 8 as measured by the Omron monitor. Morning doses of study medication were taken after the exam on study visit days, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Outcome measures

Outcome measures
Measure	Olmesartan n=384 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=424 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=426 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Incremental Change From Week 4 to Week 8 in Trough, Cuff, Seated Diastolic Blood Pressure (SDBP)	-0.8 mmHg Standard Error 0.40	-0.9 mmHg Standard Error 0.38	0.0 mmHg Standard Error 0.38

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4, Week 8

The change from Week 4 in trough SSBP at Week 8 as measured by the Omron monitor. Morning doses of study medication were taken after the exam on study visit days, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Outcome measures

Outcome measures
Measure	Olmesartan n=384 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=424 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=426 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Incremental Change From Week 4 to Week 8 in Trough, Cuff, Seated Systolic Blood Pressure (SSBP)	-1.1 mmHg Standard Error 0.66	-1.4 mmHg Standard Error 0.63	0.0 mmHg Standard Error 0.63

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4

Population: Efficacy population. Last observation carried forward. Denominator is the number of participants who have seated cuff BP measurement in each treatment group at any visit during the entire randomized treatment phase. Participants randomized to placebo-olmesartan, the measurement is after at least one dose of olmesartan.

Percentage of participants who achieved the following goals: Systolic blood pressure: \<140 mmHg, \<135 mmHg, \<130 mmHg, \<120 mmHg Diastolic blood pressure: \<90 mmHg, \<85 mmHg, \<80 mmHg Blood pressure: \<140/90 mmHg, \<135/80 mmHg, \<130/80 mmHg

Outcome measures

Outcome measures
Measure	Olmesartan n=417 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=461 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=461 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Systolic BP <140 mmHg	37.9 percentage of participants analyzed	36.7 percentage of participants analyzed	25.6 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Systolic BP <135 mmHg	28.1 percentage of participants analyzed	27.1 percentage of participants analyzed	14.1 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Systolic BP <130 mmHg	16.8 percentage of participants analyzed	16.5 percentage of participants analyzed	7.2 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Systolic BP <120 mmHg	3.1 percentage of participants analyzed	3.5 percentage of participants analyzed	2.0 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Diastolic BP <90 mmHg	39.6 percentage of participants analyzed	38.8 percentage of participants analyzed	24.5 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Diastolic BP <85 mmHg	24.2 percentage of participants analyzed	23.9 percentage of participants analyzed	13.0 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Diastolic BP <80 mmHg	10.6 percentage of participants analyzed	10.4 percentage of participants analyzed	4.6 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Blood pressure <140/90 mmHg	27.3 percentage of participants analyzed	26.5 percentage of participants analyzed	14.3 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Blood pressure <135/80 mmHg	7.4 percentage of participants analyzed	7.6 percentage of participants analyzed	2.2 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 4 Blood pressure <130/80 mmHg	5.5 percentage of participants analyzed	5.9 percentage of participants analyzed	1.5 percentage of participants analyzed

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 8

Outcome measures

Outcome measures
Measure	Olmesartan n=384 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=424 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=426 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Systolic BP <140 mmHg	41.1 percentage of participants analyzed	41.0 percentage of participants analyzed	28.9 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Systolic BP <135 mmHg	29.9 percentage of participants analyzed	30.0 percentage of participants analyzed	20.4 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Systolic BP <130 mmHg	18.2 percentage of participants analyzed	18.4 percentage of participants analyzed	13.1 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Systolic BP <120 mmHg	6.8 percentage of participants analyzed	6.6 percentage of participants analyzed	3.8 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Diastolic BP <90 mmHg	43.2 percentage of participants analyzed	42.5 percentage of participants analyzed	30.5 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Diastolic BP <85 mmHg	22.9 percentage of participants analyzed	22.9 percentage of participants analyzed	15.5 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Diastolic BP <80 mmHg	12.2 percentage of participants analyzed	11.8 percentage of participants analyzed	6.6 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Blood pressure <140/90 mmHg	32.6 percentage of participants analyzed	31.6 percentage of participants analyzed	19.5 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Blood pressure <135/80 mmHg	10.2 percentage of participants analyzed	9.9 percentage of participants analyzed	4.9 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Blood pressure <130/80 mmHg	7.6 percentage of participants analyzed	7.5 percentage of participants analyzed	4.5 percentage of participants analyzed
Percentage of Participants Achieving Blood Pressure Goals at Week 8 Blood pressure <120/80 mmHg	4.9 percentage of participants analyzed	4.7 percentage of participants analyzed	2.3 percentage of participants analyzed

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4

Population: The ABPM population was defined as all participants in the efficacy population that had valid (technically successful required at least 23 hours of ABPM data) baseline and Week 4 ABPM data.

Outcome measures

Outcome measures
Measure	Olmesartan n=108 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=118 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=118 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline in Mean 24-Hour Ambulatory Blood Pressure at Week 4 Systolic blood pressure	-7.3 mmHg Standard Error 1.08	-7.3 mmHg Standard Error 1.03	-5.9 mmHg Standard Error 1.03
Change From Baseline in Mean 24-Hour Ambulatory Blood Pressure at Week 4 Diastolic blood pressure	-4.9 mmHg Standard Error 0.70	-4.8 mmHg Standard Error 0.67	-3.7 mmHg Standard Error 0.67

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 8

Outcome measures

Outcome measures
Measure	Olmesartan n=98 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=106 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=110 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline in Mean 24-Hour Ambulatory Blood Pressure at Week 8 Systolic blood pressure	-9.1 mmHg Standard Error 1.16	-9.2 mmHg Standard Error 1.11	-5.6 mmHg Standard Error 1.09
Change From Baseline in Mean 24-Hour Ambulatory Blood Pressure at Week 8 Diastolic blood pressure	-6.1 mmHg Standard Error 0.78	-6.1 mmHg Standard Error 0.75	-3.6 mmHg Standard Error 0.73

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4

Population: The ambulatory blood pressure monitor (ABPM) population was defined as participants in the efficacy population that had valid baseline and Week 4 ABPM data. Valid (technically successful) ABPM had at least 23 hours of ABPM data.

In week 4, participants arrived at the site in the morning without having taken that day's dose of medication. Once the ambulatory blood pressure monitor (ABPM) had been applied, medication was taken and the participant wore the ABPM for a period of 24-hours. Daytime (8am to 4pm) and nighttime (10pm to 6am) systolic and diastolic blood pressure readings are summarized.

Outcome measures

Outcome measures
Measure	Olmesartan n=108 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=118 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=118 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 4 Daytime systolic blood pressure	-7.6 mmHg Standard Error 1.27	-7.5 mmHg Standard Error 1.22	-5.8 mmHg Standard Error 1.22
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 4 Daytime diastolic blood pressure	-5.4 mmHg Standard Error 0.84	-5.2 mmHg Standard Error 0.81	-3.5 mmHg Standard Error 0.81
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 4 Nighttime systolic blood pressure	-6.7 mmHg Standard Error 1.15	-6.8 mmHg Standard Error 1.10	-5.5 mmHg Standard Error 1.10
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 4 Nighttime diastolic blood pressure	-4.4 mmHg Standard Error 0.77	-4.3 mmHg Standard Error 0.74	-3.4 mmHg Standard Error 0.74

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 8

Population: The ambulatory blood pressure monitor (ABPM) population was defined as participants in the efficacy population that had valid baseline and Week 8 ABPM data. Valid (technically successful) ABPM had at least 23 hours of ABPM data.

In week 8, participants arrived at the site in the morning without having taken that day's dose of medication. Once the ambulatory blood pressure monitor (ABPM) had been applied, medication was taken and the participant wore the ABPM for a period of 24-hours. Daytime (8am to 4pm) and nighttime (10pm to 6am) systolic and diastolic blood pressure readings are summarized.

Outcome measures

Outcome measures
Measure	Olmesartan n=98 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=106 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=110 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 8 Daytime systolic blood pressure	-8.7 mmHg Standard Error 1.24	-8.7 mmHg Standard Error 1.20	-5.2 mmHg Standard Error 1.17
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 8 Daytime diastolic blood pressure	-6.2 mmHg Standard Error 0.86	-6.1 mmHg Standard Error 0.83	-3.7 mmHg Standard Error 0.82
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 8 Nighttime systolic blood pressure	-9.3 mmHg Standard Error 1.32	-9.3 mmHg Standard Error 1.27	-6.3 mmHg Standard Error 1.25
Change From Baseline in Mean Daytime (8am to 4pm) and Mean Nighttime (10pm to 6am) Ambulatory Blood Pressure at Week 8 Nighttime diastolic blood pressure	-6.2 mmHg Standard Error 0.91	-6.1 mmHg Standard Error 0.87	-4.1 mmHg Standard Error 0.86

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4

In week 4, participants arrived at the site in the morning without having taken that day's dose of medication. Once the ambulatory blood pressure monitor (ABPM) had been applied, medication was taken and the participant wore the ABPM for a period of 24-hours. Systolic and diastolic blood pressure readings taken in the final 2, 4, and 6 hours of the 24-hour ABPM cycle are summarized.

Outcome measures

Outcome measures
Measure	Olmesartan n=108 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=118 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=118 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 4 4 hour diastolic blood pressure	-5.8 mmHg Standard Error 0.85	-5.6 mmHg Standard Error 0.82	-4.1 mmHg Standard Error 0.82
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 4 2 hour systolic blood pressure	-8.7 mmHg Standard Error 1.31	-8.4 mmHg Standard Error 1.26	-6.8 mmHg Standard Error 1.26
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 4 2 hour diastolic blood pressure	-5.8 mmHg Standard Error 0.94	-5.6 mmHg Standard Error 0.90	-3.8 mmHg Standard Error 0.90
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 4 4 hour systolic blood pressure	-8.4 mmHg Standard Error 1.23	-8.3 mmHg Standard Error 1.18	-6.5 mmHg Standard Error 1.18
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 4 6 hour systolic blood pressure	-8.0 mmHg Standard Error 1.18	-8.0 mmHg Standard Error 1.13	-6.2 mmHg Standard Error 1.13
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 4 6 hour diastolic blood pressure	-5.5 mmHg Standard Error 0.83	-5.4 mmHg Standard Error 0.79	-3.9 mmHg Standard Error 0.79

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 8

In week 8, participants arrived at the site in the morning without having taken that day's dose of medication. Once the ambulatory blood pressure monitor (ABPM) had been applied, medication was taken and the participant wore the ABPM for a period of 24-hours. Systolic and diastolic blood pressure readings taken in the final 2, 4, and 6 hours of the 24-hour ABPM cycle are summarized.

Outcome measures

Outcome measures
Measure	Olmesartan n=98 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=106 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan n=110 Participants Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 8 2 hour systolic blood pressure	-10.0 mmHg Standard Error 1.56	-9.5 mmHg Standard Error 1.50	-7.2 mmHg Standard Error 1.48
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 8 2 hour diastolic blood pressure	-6.3 mmHg Standard Error 1.10	-6.0 mmHg Standard Error 1.06	-4.0 mmHg Standard Error 1.04
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 8 4 hour systolic blood pressure	-10.5 mmHg Standard Error 1.40	-10.1 mmHg Standard Error 1.35	-6.9 mmHg Standard Error 1.32
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 8 4 hour diastolic blood pressure	-7.1 mmHg Standard Error 0.96	-6.7 mmHg Standard Error 0.93	-4.1 mmHg Standard Error 0.91
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 8 6 hour systolic blood pressure	-10.0 mmHg Standard Error 1.33	-9.7 mmHg Standard Error 1.28	-6.5 mmHg Standard Error 1.25
Change From Baseline in Mean Ambulatory Blood Pressure During the Final 2, 4, and 6 Hours of the Dosing Interval at Week 8 6 hour diastolic blood pressure	-6.8 mmHg Standard Error 0.92	-6.5 mmHg Standard Error 0.89	-4.0 mmHg Standard Error 0.87

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 2

Population: The efficacy population was defined as participants who received at least 1 dose of double-blind randomized study medication and had a baseline and at least 1 post-baseline blood pressure measurement. Last observation carried forward.

The change from baseline in trough systolic and diastolic blood pressure at Week 2 as measured by the Omron monitor. Morning doses of study medication were taken after the exam, therefore exam measurements were taken when medication levels were at its lowest ('the trough'). Following a 5-minute rest period, three separate blood pressure measurements were taken with a full 2-minute (not exceeding 5 minutes) interval between measurements, with the cuff fully deflated between measurements. The mean of the 3 seated blood pressure measurements constitute the blood pressure value for the visit.

Outcome measures

Outcome measures
Measure	Olmesartan n=417 Participants Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Combined Olmesartan n=50 Participants Participants who were randomized to Olmesartan or to Placebo Followed by Olmesartan treatment arms, and received at least 1 high dose of olmesartan (40mg)	Losartan Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
Change From Baseline to Week 2 in Trough, Cuff, Seated Blood Pressure Diastolic blood pressure	-8.3 mmHg Standard Error 0.42	-4.0 mmHg Standard Error 1.22	—
Change From Baseline to Week 2 in Trough, Cuff, Seated Blood Pressure Systolic blood pressure	-11.9 mmHg Standard Error 0.65	-3.3 mmHg Standard Error 1.87	—

Adverse Events

Olmesartan

Serious events: 0 serious events

Other events: 133 other events

Deaths: 0 deaths

Placebo Followed by Olmesartan

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Losartan

Serious events: 4 serious events

Other events: 148 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Olmesartan n=420 participants at risk Olmesartan 20 mg once daily for four weeks followed by 40mg one daily for four weeks.	Placebo Followed by Olmesartan n=52 participants at risk Placebo capsule of olmesartan once daily for 2 weeks, followed by olmesartan 20 mg once daily for two weeks, followed by olmesartan 40 mg for 4 weeks	Losartan n=469 participants at risk Losartan 50 mg once daily for four weeks, followed by losartan 100 mg once daily for four weeks
General disorders Non-cardiac chest pain	0.00% 0/420 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.00% 0/52 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.21% 1/469 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/420 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.00% 0/52 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.21% 1/469 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication
Nervous system disorders Cerebrovasular accident	0.00% 0/420 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.00% 0/52 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.21% 1/469 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication
Infections and infestations Urinary tract infection	0.00% 0/420 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.00% 0/52 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication	0.21% 1/469 • Day 1 to Week 8, or until the adverse event resolved or the condition stabilized. Safety population includes all participants who received at least 1 dose of double-blind randomized study medication

Other adverse events

Additional Information

Robert Dubiel, PharmD

Daiichi Sankyo, Inc.

Phone: 973-944-2963

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reflects the following restrictive language in the Clinical Study Agreements: "If identified by DSI, any of DSI's confidential information as defined herein shall be deleted…Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publication prepared by the Study Site."
Publication restrictions are in place

Restriction type: OTHER