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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01150357
First received: June 23, 2010
Last updated: September 15, 2015
Last verified: September 2015

June 23, 2010
September 15, 2015
June 2010
August 2014   (final data collection date for primary outcome measure)
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Endpoint (Phase 1) [ Time Frame: Baseline to endpoint (Week 4 or Last observation carried forward (LOCF)) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 to endpoint (Week 8 or LOCF) ] [ Designated as safety issue: No ]
    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.
In Phase 1 (dose response phase), change in msSBP from the baseline to end of phase 1. In Phase 2 (placebo controlled phase), change in msSBP from at end of Phase 1 to the end of Phase 2 Time Frame: Phase 1, 4 weeks, Phase 2, 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01150357 on ClinicalTrials.gov Archive Site
  • Number of Participants With Adverse Events and Serious Adverse Events From Baseline to Week 4 (Phase 1) [ Time Frame: Baseline up to Week 4 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: From Week 4 to Week 8 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline to endpoint (Week 4 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 to endpoint (Week 8 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to endpoint (Week 4 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 to endpoint (Week 8 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to endpoint (Week 4 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to endpoint (Week 4 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to endpoint (Week 4 or LOCF) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to endpoint (Week 4 or LOCF) ] [ Designated as safety issue: No ]
    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.
  • Change in mean sitting diastolic blood pressure (msDBP) from baseline to end of Phase 1 Time Frame: 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Change in msDBP from end of Phase 1 to end of phase [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Calculated mean arterial pressure (MAP) change from baseline to end of Phase 1 Time Frame [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Calculate MAP change from end of Phase 1 to end of Phase 2 Time Frame [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • To explore the effect of aliskiren at low, mid and high doses on the 24 hour ambulatory blood pressure monitoring (ABPM) profiles. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
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Safety and Efficacy of Aliskiren in Pediatric Hypertensive Patients 6-17 Years of Age
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypertension
  • Drug: Aliskiren (6.25/12.5/25 mg)
    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.
  • Drug: Aliskiren (37.5/75/150 mg)
    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.
  • Drug: Aliskiren (150/300/600 mg)
    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.
  • Experimental: Low Dose Aliskiren
    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.
    Intervention: Drug: Aliskiren (6.25/12.5/25 mg)
  • Experimental: Mid dose
    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.
    Intervention: Drug: Aliskiren (37.5/75/150 mg)
  • Experimental: High dose
    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.
    Intervention: Drug: Aliskiren (150/300/600 mg)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
267
August 2014
August 2014   (final data collection date for primary outcome measure)

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

Both
6 Years to 17 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Germany,   Guatemala,   Hungary,   Poland,   Puerto Rico,   Slovakia,   Turkey
France
 
NCT01150357
CSPP100A2365, 2009-017028-22
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP