Hypertension
Conditions
Keywords
Treatment of hypertension or high blood pressure in children ages 1-16 years.
Brief summary
This study assesses the efficacy and safety of olmesartan medoxomil in children ages 1-16 with high blood pressure. After a 5-week blinded treatment period of up to 5 weeks participants can continue to take olmesartan medoxomil (OM) for up to an additional 46 weeks.
Detailed description
This was a randomized, multicenter, double-blind, parallel-group, prospective dose-ranging study in subjects 1 to 16 years of age with hypertension. Subjects were enrolled into 1 of 3 cohorts based on age and race. Subjects 6 to 16 years of age were enrolled into Cohort A. Subjects enrolled into Cohort A were stratified by age with approximately half aged 6 to 12 years and the remainder aged 13 to 16 years. Approximately 15% of the subjects in Cohort A were to be Black or of African descent. When a minimum of 28 Black subjects were randomized into Cohort A, enrollment in Cohort B was started. Black subjects only, 6 to 16 years of age, were enrolled into Cohort B. For Cohorts A and B body weight of any patient was \>=20Kg. Seated systolic blood pressure (SeSBP) was \>=95th percentile for gender and height-for-age, or \>=90th percentile if the patient is diabetic, or has glomerular kidney disease, or has a family history of hypertension. Patients with symptomatic hypertension requiring immediate established therapy, or who are above 2 standard deviations (SD) above the 99th percentile did not participate in the study. Subjects 1 to 5 years of age were enrolled into Cohort C regardless of race. Body weight of any patient was \>=5Kg. SeSBP was \>=95th percentile for gender and height-for-age, or \>=90th percentile if the patient is diabetic, or has glomerular kidney disease, or has a family history of hypertension. Patients on stable doses of concomitant antihypertensive agents including calcium channel blockers and/or diuretics only are permitted to enroll. Patients with symptomatic hypertension requiring immediate established therapy, or who are above 2 SD above the 99th percentile did not participate in the study. The study comprised four periods. Period I was a wash-out period from Week -1 to randomization. Subjects were randomized to treatment sequences carried through the remainder of the study. Period II was a three-week, double-blind, dose-ranging period for Cohorts A and B, beginning at Day 1 and ending at the end of Week 3. In Cohorts A and B, subjects received either low-dose or high-dose olmesartan (OM) once daily. In Cohort C, Period II was an open-label OM treatment period where all subjects received 0.3 mg/kg OM per day. Period III was a double-blind, placebo-controlled withdrawal period beginning at Week 4 and ending after 1 or 2 weeks, depending on the seated blood pressure measurement at each weekly study visit. Subjects either continued their Period II OM regimen or switched to placebo based on the initial randomization scheme. Period IV was a 46-week open-label extension period.
Interventions
DRUGolmesartan medoxomil
Cohorts A and B: 2.5mg to 40mg olmesartan, as a suspension (depending on weight), once daily. Tablets were used to prepare a suspension. Cohort C: 0.3mg/kg olmesartan ,as a suspension, once daily
DRUGplacebo
Cohorts A, B, C: placebo, once daily
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* The patient's seated systolic BP (SeSBP) will be greater than or equal to 95th percentile for gender and height-for- age, or greater than or equal to 90th percentile if the patient is diabetic, or has glomerular kidney disease, or has a family history of hypertension. * Negative for hepatitis B and C * Negative for HIV
Exclusion criteria
* Patient should not have serious other conditions that could interfere with the analysis of the results or that could interfere with the well-being of the patient in the trial. * Known sensitivity to olmesartan medoxomil * Taking prohibited medication * Consumed greater than 180 mg of caffeine daily * Malignant hypertension * History of congestive heart failure, cardiomyopathy, or obstructive valve disease * Renal transplant within the previous 6 months * Severe nephritic syndrome not in remission
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Day 0 to 3 weeks | The efficacy dose response change in trough seated systolic blood pressure (both non-weight adjusted and weight adjusted results) from baseline to the end of the dose-ranging period (Period 2). Non-weight adjusted dose was the fixed olmesartan medoxomil dose; weight adjusted dose calculated mg of olmesartan medoxomil per kg of weight at baseline. |
| Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Day 0 (baseline) to 3 weeks | Mean change from baseline to the end of the dose ranging period in systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Week 3 (period 3 baseline) to week 5 (end of Period 3) | Mean change from period 3 baseline (completion of the dose adjustment period and prior to starting the treatment of period 3) to the end of period 3 (double-blind placebo-controlled period) in seated systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined. |
| Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Day 0 to week 51 (end of study) | Mean change from baseline to the end of the open label Period 4 in seated systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined. |
Countries
Argentina, Brazil, Chile, Colombia, India, Kenya, Peru, South Africa, Uganda, United States, Zambia
Participant flow
Pre-assignment details
Period 1 was a screening, wash-out period of approximately two weeks. All participants were included in the screening, wash-out period and during this period no intervention was administered.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: High Dose OM Subgroup of Cohort A (6-16 years old with a limit on the number of Black participants) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period). | 95 |
| Cohort A: Low Dose OM Subgroup of Cohort A (6-16 years old with a limit on the number of Black participants) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period). | 95 |
| Cohort B: High Dose OM Subgroup of Cohort B (6-16 years old comprised exclusively of Black participants) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period). | 56 |
| Cohort B: Low Dose OM Subgroup of Cohort B (6-16 years old comprised exclusively of Black participants) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period). | 56 |
| Cohort C: OM (Olmesartan Medoxomil) Cohort C (1-5 years old) was given olmesartan medoxomil (OM) 0.3 mg/kg in Period 2 (open-label period) and a subgroup of Cohort C was given that dose of OM during Period 3 (double-blind, placebo-controlled period). In Period 4 (open-label period), all of Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two week the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled. | 60 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 2 - Double-Blind Dose Response | Adverse Event | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 - Double-Blind Dose Response | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Period 2 - Double-Blind Dose Response | non-compliance | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 - Double-Blind Dose Response | Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 - Double-Blind Dose Response | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 - Double-Blind Dose Response | Protocol Violation | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 - Double-Blind Dose Response | The blood pressure goal was met | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 3: Double-blind, Withdrawal | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 3: Double-blind, Withdrawal | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 3: Double-blind, Withdrawal | Met blood pressure goal | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 3: Double-blind, Withdrawal | Other | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Period 3: Double-blind, Withdrawal | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 3: Double-blind, Withdrawal | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 4: Open Label | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Period 4: Open Label | Increased blood pressure | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 4: Open Label | Lost to Follow-up | 0 | 0 | 0 | 0 | 17 | 0 | 0 | 0 | 0 | 7 | 0 | 0 |
| Period 4: Open Label | Non-compliance with protocol | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 4 | 0 | 0 |
| Period 4: Open Label | Other | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 |
| Period 4: Open Label | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Period 4: Open Label | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 4: Open Label | Withdrawal by Subject | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A: High Dose OM | Cohort A: Low Dose OM | Cohort B: High Dose OM | Cohort B: Low Dose OM | Cohort C: OM (Olmesartan Medoxomil) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 2.97 | 12.3 years STANDARD_DEVIATION 2.98 | 12.2 years STANDARD_DEVIATION 2.83 | 12.8 years STANDARD_DEVIATION 2.42 | 3.4 years STANDARD_DEVIATION 1.45 | 12.3 years STANDARD_DEVIATION 2.85 |
| Height | 153.3 cm STANDARD_DEVIATION 18.46 | 155.1 cm STANDARD_DEVIATION 19.12 | 154.2 cm STANDARD_DEVIATION 17.83 | 156.1 cm STANDARD_DEVIATION 14.21 | 98.3 cm STANDARD_DEVIATION 12.92 | 154.6 cm STANDARD_DEVIATION 17.79 |
| Race/Ethnicity, Customized Latino/Hispanic | 42 Participants | 47 Participants | 0 Participants | 1 Participants | 27 Participants | 117 Participants |
| Race/Ethnicity, Customized non-Latino/Hispanic | 53 Participants | 48 Participants | 56 Participants | 55 Participants | 33 Participants | 245 Participants |
| Seated diastolic blood pressure | 76.3 mm Hg STANDARD_DEVIATION 8.09 | 78.1 mm Hg STANDARD_DEVIATION 8.17 | 79.2 mm Hg STANDARD_DEVIATION 7.08 | 79.4 mm Hg STANDARD_DEVIATION 9.05 | 72.7 mm Hg STANDARD_DEVIATION 8.74 | 78.0 mm Hg STANDARD_DEVIATION 8.18 |
| Seated Systolic blood pressure | 129.1 mm Hg STANDARD_DEVIATION 8.32 | 129.5 mm Hg STANDARD_DEVIATION 9.1 | 130.8 mm Hg STANDARD_DEVIATION 9.73 | 131.7 mm Hg STANDARD_DEVIATION 9.12 | 115.2 mm Hg STANDARD_DEVIATION 8.74 | 130.0 mm Hg STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 33 Participants | 35 Participants | 35 Participants | 20 Participants | 26 Participants | 149 Participants |
| Sex: Female, Male Male | 62 Participants | 60 Participants | 21 Participants | 36 Participants | 34 Participants | 213 Participants |
| Weight | 68.0 kg STANDARD_DEVIATION 34.22 | 78.9 kg STANDARD_DEVIATION 41.85 | 66.2 kg STANDARD_DEVIATION 32.39 | 68.1 kg STANDARD_DEVIATION 34.36 | 16.9 kg STANDARD_DEVIATION 6.61 | 71.1 kg STANDARD_DEVIATION 36.72 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 95 | 46 / 95 | 15 / 48 | 6 / 45 | 9 / 45 | 6 / 44 | 128 / 178 | 9 / 56 | 12 / 56 | 4 / 26 | 1 / 28 | 2 / 27 | 1 / 26 | 56 / 103 | 12 / 59 | 4 / 29 | 8 / 28 | 46 / 57 |
| serious Total, serious adverse events | 2 / 95 | 1 / 95 | 0 / 48 | 0 / 45 | 0 / 45 | 0 / 44 | 20 / 179 | 0 / 56 | 0 / 56 | 1 / 26 | 0 / 28 | 0 / 27 | 0 / 26 | 7 / 104 | 0 / 59 | 0 / 29 | 0 / 29 | 6 / 57 |
Outcome results
Primary
Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks)
The efficacy dose response change in trough seated systolic blood pressure (both non-weight adjusted and weight adjusted results) from baseline to the end of the dose-ranging period (Period 2). Non-weight adjusted dose was the fixed olmesartan medoxomil dose; weight adjusted dose calculated mg of olmesartan medoxomil per kg of weight at baseline.
Time frame: Day 0 to 3 weeks
Population: The number of participants includes all randomized to Cohort A, Cohort B and a combination of the two cohorts. The Last Observation Carried Forward method was used in the linear regression analysis for the change in the seated systolic blood pressure from baseline to the end of three weeks.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Non-weight adjusted dosage | -0.69 mm Hg | Standard Error 0.202 |
| Cohort A | Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Weight adjusted dosage | -8.97 mm Hg | Standard Error 2.054 |
| Cohort B | Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Non-weight adjusted dosage | -0.85 mm Hg | Standard Error 0.282 |
| Cohort B | Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Weight adjusted dosage | -7.17 mm Hg | Standard Error 3.19 |
| Cohorts A + B | Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Non-weight adjusted dosage | -0.75 mm Hg | Standard Error 0.165 |
| Cohorts A + B | Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) | Weight adjusted dosage | -8.36 mm Hg | Standard Error 1.75 |
Comparison: Non-weight adjusted dosagep-value: 0.0008Regression, Linear
Comparison: Weight adjusted dosagep-value: <0.0001Regression, Linear
Comparison: Non-weight adjusted dosagep-value: 0.0032Regression, Linear
Comparison: Weight adjusted dosagep-value: 0.0265Regression, Linear
Comparison: Non-weight adjusted dosagep-value: <0.0001Regression, Linear
Comparison: Weight adjusted dosagep-value: <0.0001Regression, Linear
Primary
Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks)
Mean change from baseline to the end of the dose ranging period in systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined.
Time frame: Day 0 (baseline) to 3 weeks
Population: The Intent-to-Treat (ITT) population for Period II of the study was defined as subjects who took at least one dose of study medication and had study baseline and at least one seated systolic, or diastolic blood pressure measurement after taking study medication. The Last Observation carried forward was used
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Systolic Blood Pressure | -7.76 mm Hg | Standard Deviation 9.18 |
| Cohort A | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Diastolic Blood Pressure | -5.52 mm Hg | Standard Deviation 8.058 |
| Cohort B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Systolic Blood Pressure | -12.58 mm Hg | Standard Deviation 10.157 |
| Cohort B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Diastolic Blood Pressure | -9.50 mm Hg | Standard Deviation 9.757 |
| Cohorts A + B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Systolic Blood Pressure | -4.73 mm Hg | Standard Deviation 11.483 |
| Cohorts A + B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Diastolic Blood Pressure | -3.49 mm Hg | Standard Deviation 8.844 |
| Cohort B: High Dose OM | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Systolic Blood Pressure | -10.68 mm Hg | Standard Deviation 9.259 |
| Cohort B: High Dose OM | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Diastolic Blood Pressure | -7.58 mm Hg | Standard Deviation 8.172 |
| Cohorts A + B: Low Dose OM | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Systolic Blood Pressure | -6.63 mm Hg | Standard Deviation 10.17 |
| Cohorts A + B: Low Dose OM | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Diastolic Blood Pressure | -4.76 mm Hg | Standard Deviation 8.389 |
| Cohorts A + B: High Dose OM | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Systolic Blood Pressure | -11.87 mm Hg | Standard Deviation 9.843 |
| Cohorts A + B: High Dose OM | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 Weeks) | Change in Diastolic Blood Pressure | -8.78 mm Hg | Standard Deviation 9.216 |
Comparison: A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: 0.0008Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: 0.0026Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: 0.0032Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: 0.0125Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: <0.0001Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: <0.0001Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: <0.0001Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: <0.0001Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: 0.0265Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: 0.0084Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: <0.0001Regression, Linear
Comparison: A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.p-value: <0.0001Regression, Linear
Secondary
Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study)
Mean change from baseline to the end of the open label Period 4 in seated systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined.
Time frame: Day 0 to week 51 (end of study)
Population: Intent to treat population includes participants with at least one visit in Period 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Systolic Blood Pressure | -10.8 mm Hg | Standard Deviation 9.75 |
| Cohort A | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Diastolic Blood Pressure | -7.4 mm Hg | Standard Deviation 9.31 |
| Cohort B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Systolic Blood Pressure | -7.7 mm Hg | Standard Deviation 12.71 |
| Cohort B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Diastolic Blood Pressure | -5.1 mm Hg | Standard Deviation 9.45 |
| Cohorts A + B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Systolic Blood Pressure | -9.7 mm Hg | Standard Deviation 11.01 |
| Cohorts A + B | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Diastolic Blood Pressure | -6.6 mm Hg | Standard Deviation 9.41 |
Secondary
Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study)
Mean change from baseline to the end of the open label Period 4 in seated systolic and diastolic blood pressure readings for Cohort C.
Time frame: Day 0 to week 51 week (end of study)
Population: 57=the number of participants who received medication in Period 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Systolic Blood Pressure | -15.7 mm Hg | Standard Deviation 9.83 |
| Cohort A | Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) | Change in Diastolic Blood Pressure | -13.3 mm Hg | Standard Deviation 11.18 |
Secondary
Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3
Mean change from period 3 baseline (completion of the dose adjustment period and prior to starting the treatment of period 3) to the end of period 3 (double-blind placebo-controlled period) in seated systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined.
Time frame: Week 3 (period 3 baseline) to week 5 (end of Period 3)
Population: Intent to treat population defined as subjects who finished Period 2, had the end of Period 2 seated systolic or diastolic blood pressure measurement, took the Period 3 study medication for at least one week, and had the end of Period 3 seated systolic or diastolic blood pressure measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Systolic Blood Pressure | 0.43 mm Hg | Standard Deviation 9.46 |
| Cohort A | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Diastolic Blood Pressure | 0.24 mm Hg | Standard Deviation 8.12 |
| Cohort B | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Systolic Blood Pressure | 4.93 mm Hg | Standard Deviation 9.62 |
| Cohort B | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Diastolic Blood Pressure | 4.43 mm Hg | Standard Deviation 10.15 |
| Cohorts A + B | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Systolic Blood Pressure | 1.37 mm Hg | Standard Deviation 9.5 |
| Cohorts A + B | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Diastolic Blood Pressure | 1.94 mm Hg | Standard Deviation 7.1 |
| Cohort B: High Dose OM | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Systolic Blood Pressure | 3.79 mm Hg | Standard Deviation 10 |
| Cohort B: High Dose OM | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Diastolic Blood Pressure | 3.25 mm Hg | Standard Deviation 8.74 |
| Cohorts A + B: Low Dose OM | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Systolic Blood Pressure | 0.77 mm Hg | Standard Deviation 9.451 |
| Cohorts A + B: Low Dose OM | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Diastolic Blood Pressure | 0.85 mm Hg | Standard Deviation 7.79 |
| Cohorts A + B: High Dose OM | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Systolic Blood Pressure | 4.50 mm Hg | Standard Deviation 9.745 |
| Cohorts A + B: High Dose OM | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Change in Diastolic Blood Pressure | 3.99 mm Hg | Standard Deviation 9.627 |
Comparison: Analysis of systolic blood pressure. Null hypothesis of no treatment difference was tested.p-value: 0.009395% CI: [-6.27, -0.89]ANCOVA
Comparison: Analysis for diastolic blood pressure. The null hypothesis of no treatment difference was tested.p-value: 0.005295% CI: [-5.92, -1.05]ANCOVA
Comparison: Analysis of systolic blood pressure. Null hypothesis of no treatment difference was tested.p-value: 0.13395% CI: [-5.93, 0.79]ANCOVA
Comparison: Analysis for diastolic blood pressure. The null hypothesis of no treatment difference was tested.p-value: 0.344295% CI: [-4.27, 1.5]ANCOVA
Comparison: For seated systolic blood pressure the null hypothesis of no treatment difference was testedp-value: 0.002995% CI: [-5.24, -1.09]ANCOVA
Comparison: For seated diastolic blood pressure the null hypothesis of no treatment difference was tested.p-value: 0.003295% CI: [-4.65, -0.95]ANCOVA
Secondary
Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3
Mean change from period 3 baseline (completion of the dose adjustment period and prior to starting the treatment of period 3) to the end of period 3 (double-blind placebo-controlled period) in seated systolic and diastolic blood pressure readings for Cohort C.
Time frame: Week 3 (period 3 baseline) to week 5 (end of Period 3)
Population: Intent to treat population defined as subjects who finished Period 2, had the end of Period 2 seated systolic or diastolic blood pressure measurement, took the Period 3 study medication for at least one week, and had the end of Period 3 seated systolic or diastolic blood pressure measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Seated Systolic Blood Pressure | 1.36 mm Hg | Standard Deviation 8.994 |
| Cohort A | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Seated Diastolic Blood Pressure | 0.31 mm Hg | Standard Deviation 8.556 |
| Cohort B | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Seated Systolic Blood Pressure | 4.95 mm Hg | Standard Deviation 8.568 |
| Cohort B | Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 | Seated Diastolic Blood Pressure | 3.77 mm Hg | Standard Deviation 7.203 |
Comparison: For seated systolic blood pressure the null hypothesis of no treatment difference was tested.p-value: 0.211395% CI: [-7.29, 1.65]ANCOVA
Comparison: For seated diastolic blood pressure the null hypothesis of no treatment difference was tested.p-value: 0.149695% CI: [-6.92, 1.09]ANCOVA