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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01150357
• Other study ID #: CSPP100A2365
• Secondary ID: 2009-017028-22
• Status: Completed
• Phase: Phase 3
• First received: June 23, 2010
• Last updated: September 15, 2015
• Start date: June 2010
• Est. completion date: August 2014

Study information

• Verified date: September 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical DevicesSlovakia: State Institute for Drug ControlTurkey: General Directorate of Pharmaceuticals and PharmacyHungary: National Institute of PharmacyPoland: The Central Register of Clinical TrialsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Germany	Novartis Investigative Site	Marburg
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Nyiregyhaza
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Veszprem
Poland	Novartis Investigative Site	Warszawa
Puerto Rico	Novartis Investigative Site	San Juan
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Myjava
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Trnava
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Izmir
United States	Novartis Investigative Site	Amarillo	Texas
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Charleston	West Virginia
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Dalton	Georgia
United States	Novartis Investigative Site	Hackensack	New Jersey
United States	Novartis Investigative Site	Hattiesburg	Mississippi
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Lewiston	Idaho
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Park Ridge	Illinois
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Guatemala,  Hungary,  Poland,  Puerto Rico,  Slovakia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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))	No
Primary	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)	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No