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

• Least Squares Mean Change From Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 Weeks) [ Time Frame: Day 0 to 3 weeks ] [ Designated as safety issue: No ]
  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) [ Time Frame: Day 0 (baseline) to 3 weeks ] [ Designated as safety issue: No ]
  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.
  
  

• Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 [ Time Frame: Week 3 (period 3 baseline) to week 5 (end of Period 3) ] [ Designated as safety issue: No ]
  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 Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3 [ Time Frame: Week 3 (period 3 baseline) to week 5 (end of Period 3) ] [ Designated as safety issue: No ]
  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.
  
  
• Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) [ Time Frame: Day 0 to week 51 (end of study) ] [ Designated as safety issue: No ]
  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.
  
  
• Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) [ Time Frame: Day 0 to week 51 week (end of study) ] [ Designated as safety issue: No ]
  Mean change from baseline to the end of the open label Period 4 in seated systolic and diastolic blood pressure readings for Cohort C.
  
  

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.