Assessment of Efficacy and Safety of Olmesartan Medoxomil in Children and Adolescent Patients With High Blood Pressure

Study Overview
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Brief Summary
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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
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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.

Official Title
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Dose-ranging Study to Evaluate the Safety and Efficacy of Olmesartan Medoxomil in Children and Adolescents With Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: olmesartan medoxomil
* Drug: placebo
* Drug: olmesartan medoxomil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 2<br>For Cohorts A and B, olmesartan medoxomil suspension 2.5 mg to 40 mg in patients 6-16 years old, depending on weight. For Cohort C, olmesartan medoxomil suspension 0.3 mg/kg to in patients 1-5 years old. | Drug: olmesartan medoxomil<br>* 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<br>* Other names: Benicar (olmesartan medoxomil);|
| Experimental: Period 3<br>Cohorts A, B, C - olmesartan medoxomil suspension or placebo taken once daily. Olmesartan medoxomil dose continued as in previous period. | Drug: olmesartan medoxomil<br>* 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<br>* Other names: Benicar (olmesartan medoxomil);Drug: placebo<br>* Cohorts A, B, C: placebo, once daily<br>|
| Experimental: Period 4<br>Cohorts A and B: Open label olmesartan medoxomil suspension or tablets 10mg - 40 mg Cohort C: Open label olmesartan medoxomil suspension 0.3 mg/kg - 0.6 mg/kg | Drug: olmesartan medoxomil<br>* Cohorts A and B: Open label olmesartan medoxomil suspension or tablets 10mg - 40 mg. Tablets were used to prepare the suspension or were given directly. Cohort C: Open label olmesartan medoxomil suspension 0.3 mg/kg - 0.6 mg/kg<br>* Other names: Benicar (olmesartan medoxomil);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 0 to 3 weeks | 
| 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. | Day 0 (baseline) to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 3 (period 3 baseline) to week 5 (end of Period 3) | 
| 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. | Week 3 (period 3 baseline) to week 5 (end of Period 3) | 
| 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. | Day 0 to week 51 (end of study) | 
| 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. | Day 0 to week 51 week (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment of hypertension or high blood pressure in children ages 1-16 years.