Safety and Efficacy of Aliskiren in Pediatric Hypertensive Patients 6-17 Years of Age

Study Overview
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Brief Summary
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This double-blind 8 week study will evaluate dose response, efficacy (blood pressure lowering effect) and safety of aliskiren in children 6 - 17 years old with hypertension at low, mid and high weight-based doses. The low dose ranges from 6.25 mg to 25 mg of aliskiren, the mid dose ranges from 37.5 mg to 150 mg of aliskiren and the high dose ranges from 150 mg to 600 mg of aliskiren. This study is being conducted to support monotherapy registration of aliskiren for the treatment of hypertension in children 6-17 years of age.

Official Title
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A Multicenter, Randomized, Double-blind, 8 Week Study to Evaluate the Dose Response, Efficacy and Safety of Aliskiren in Pediatric Hypertensive Patients 6-17 Years of Age

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren (6.25/12.5/25 mg)
* Drug: Aliskiren (37.5/75/150 mg)
* Drug: Aliskiren (150/300/600 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of hypertension as defined in the NHLBI 4th Report, 2004 msSBP (mean of 3 measurements) must be ≥ 95th percentile for age, gender and height, at Visit 2 (randomization) measurement as defined by the NHLBI 4th Report, 2004 Exclusion Criteria: Patient receiving immunosuppressant medication (e.g. cyclosporine, MMF, etc) other than oral/topical steroids, for any medical condition Current diagnosis of heart failure (NYHA Class II-IV) or history of cardiomyopathy or obstructive valvular disease msSBP ≥ 25% above the 95th percentile Second or third degree heart block without a pacemaker AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range Total bilirubin > 2 times the upper limit of the reference range Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz formula to estimate glomerular filtration rate [GFR]), based on the serum creatinine concentration obtained at the screening visit) WBC count < 3000/mm³ Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Low Dose Aliskiren<br>Participants received body-weight stratified dose of aliskiren capsules (6.25/12.5/25 mg) once daily. Participants whose body weight ≥ 20 kilogram (kg) to less than < 50 kg received 6.25 mg; ≥50 kg and < 80 kg received 12.5 mg and ≥ 80 kg and ≤ 150 kg received 25 mg of aliskiren. | Drug: Aliskiren (6.25/12.5/25 mg)<br>* Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet). For the low dose arm, participants used one or more of the 6.25 mg capsule (containing 2 minitablets) once daily to reach the body-weight stratified dose of aliskiren.<br>|
| Experimental: Mid dose<br>Participants received body-weight stratified dose of aliskiren capsules (37.5/75/150 mg) once daily. Participants whose body weight ≥ 20 kg to < 50 kg received 37.5 mg; ≥50 kg and < 80 kg received 75 mg and ≥ 80 kg and ≤ 150 kg received 150 mg of aliskiren. | Drug: Aliskiren (37.5/75/150 mg)<br>* Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet). For the medium dose arm, participants used one or more of the 37.5 mg capsule (containing 12 minitablets) once daily to reach the body- weight stratified dose of aliskiren.<br>|
| Experimental: High dose<br>Participants received body-weight stratified dose of aliskiren capsules (150/300/600 mg) once daily. Participants whose body weight ≥ 20 kg to < 50 kg received 150 mg; ≥50 kg and < 80 kg received 300 mg and ≥ 80 kg and ≤ 150 kg received 600 mg of aliskiren. | Drug: Aliskiren (150/300/600 mg)<br>* Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet). For the high dose arm, participants used one or more of the 150 mg capsule (containing 48 minitablets) once daily to reach the body- weight stratified dose of aliskiren.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Endpoint (Phase 1) | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit. | Baseline to endpoint (Week 4 or Last observation carried forward (LOCF)) | 
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Week 4 to Endpoint (Phase 2) | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit. | Week 4 to endpoint (Week 8 or LOCF) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events and Serious Adverse Events From Baseline to Week 4 (Phase 1) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. | Baseline up to Week 4 | 
| Number of Participants With Adverse Events and Serious Adverse Events From Week 4 to Week 8 (Phase 2) | AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. | From Week 4 to Week 8 | 
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Endpoint (Phase 1) | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit. | Baseline to endpoint (Week 4 or LOCF) | 
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Week 4 to Endpoint (Phase 2) | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit. | Week 4 to endpoint (Week 8 or LOCF) | 
| Change From Baseline in Mean Arterial Pressure (MAP) at Endpoint (Phase 1) | MAP was defined as the average arterial pressure during a single cardiac cycle. The MAP was measured as sum of diastolic blood pressure (DBP) and one third of difference between systolic blood pressure (SBP) and DBP i.e. MAP = DBP+1/3*(SBP-DBP). | Baseline to endpoint (Week 4 or LOCF) | 
| Change in Mean Arterial Pressure (MAP) From Week 4 to Endpoint (Phase 2) | MAP was defined as the average arterial pressure during a single cardiac cycle. The MAP was measured as sum of DBP and one third of difference between SBP and DBP i.e. MAP = DBP+1/3*(SBP-DBP). | Week 4 to endpoint (Week 8 or LOCF) | 
| Percentage of Participants Achieving a Positive Treatment Response at Endpoint (Phase 1) | Treatment responders were defined as participants with msSBP less than 95th percentile (for age, gender and height) or a 7 mmHg decrease in msSBP from the baseline. | Baseline to endpoint (Week 4 or LOCF) | 
| Change From Baseline in Mean Ambulatory Systolic and Diastolic Blood Pressure (MASBP and MADBP) at Endpoint (Phase 1) | Ambulatory Blood Pressure Monitoring (ABPM) was performed over a 24-hour period using an automatic ABPM device to record the blood pressure as per study defined criteria. The participants who were selected for this evaluation wore the ABPM device for 24 hours, returned to the clinic upon completion of the 24-hour monitoring period for removal of device and BP assessments. The ABPM device was pre-set to collect readings every 20 minutes. Mean hourly systolic and diastolic blood pressure were calculated for each participant at post dosing 1 - 24 hours. | Baseline to endpoint (Week 4 or LOCF) | 
| Change From Baseline in Mean Ambulatory Systolic Blood Pressure (MASBP) During Day and Night at Week 4 (Phase 1) | ABPM was performed over a 24-hour period using an automatic ABPM device to record the blood pressure as per study defined criteria. Day time was defined as the average of the hourly means between 6 am and 10 pm while the night time mean was the average of the hourly means between 10 pm and 6 am. | Baseline to Week 4 | 
| Change From Baseline in Mean Ambulatory Blood Pressure (MABP) in Dipper Participants at Endpoint (Phase 1) | ABPM was performed over a 24-hour period using an automatic ABPM device to record the blood pressure as per study defined criteria. Dippers were defined as those participants in whom there was a decrease in mean night time (6pm - 6am) ABPM more than or equal to (≥ ) 10% as compared to average daytime (6am -6pm) ABPM. | Baseline to endpoint (Week 4 or LOCF) | 
| Change From Baseline in Mean Ambulatory Blood Pressure (MABP) in Non--Dipper Participants at Endpoint (Phase 1) | ABPM was performed over a 24-hour period using an automatic ABPM device to record the blood pressure as per study defined criteria. Non-dippers were defined as those participants in whom there was a decrease in mean night time ABPM less than 10% as compared to average daytime ABPM. | Baseline to endpoint (Week 4 or LOCF) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric hypertension, primary hypertension, secondary hypertension