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

Phase 3

Completed

Conditions: Hypertension

Interventions: Drug: Aliskiren (6.25/12.5/25 mg)
Drug: Aliskiren (37.5/75/150 mg)
Drug: Aliskiren (150/300/600 mg)

Registration Number: NCT01150357

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 267

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Dose Aliskiren	Aliskiren (6.25/12.5/25 mg)	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.
Mid dose	Aliskiren (37.5/75/150 mg)	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.
High dose	Aliskiren (150/300/600 mg)	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or Last observation carried forward (LOCF))	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.
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Week 4 to Endpoint (Phase 2)	Week 4 to endpoint (Week 8 or LOCF)	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events and Serious Adverse Events From Baseline to Week 4 (Phase 1)	Baseline up to Week 4	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.
Number of Participants With Adverse Events and Serious Adverse Events From Week 4 to Week 8 (Phase 2)	From Week 4 to Week 8	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.
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or LOCF)	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.
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Week 4 to Endpoint (Phase 2)	Week 4 to endpoint (Week 8 or LOCF)	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.
Change From Baseline in Mean Arterial Pressure (MAP) at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or LOCF)	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).
Change in Mean Arterial Pressure (MAP) From Week 4 to Endpoint (Phase 2)	Week 4 to endpoint (Week 8 or LOCF)	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).
Percentage of Participants Achieving a Positive Treatment Response at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or LOCF)	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.
Change From Baseline in Mean Ambulatory Systolic and Diastolic Blood Pressure (MASBP and MADBP) at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or LOCF)	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.
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (MASBP) During Day and Night at Week 4 (Phase 1)	Baseline to Week 4	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.
Change From Baseline in Mean Ambulatory Blood Pressure (MABP) in Dipper Participants at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or LOCF)	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.
Change From Baseline in Mean Ambulatory Blood Pressure (MABP) in Non--Dipper Participants at Endpoint (Phase 1)	Baseline to endpoint (Week 4 or LOCF)	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.