Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A multicenter, 52 to 104 week extension study to evaluate the long term growth and development of pediatric hypertensive patients 6–17 years of age treated previously with aliskiren

    Summary
    EudraCT number
    		 2011-004411-22
    Trial protocol
    		 Outside EU/EEA   SK   PL  
    Global end of trial date
    02 Aug 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Aug 2020
    First version publication date
    19 Aug 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CSPP100A2365E2
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01420068
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Aug 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Aug 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the long term growth and development of pediatric hypertensive patients aged 6 – 17 years when treated previously with aliskiren
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Aug 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    Slovakia: 24
    Country: Number of subjects enrolled
    Turkey: 1
    Country: Number of subjects enrolled
    United States: 49
    Country: Number of subjects enrolled
    Guatemala: 7
    Country: Number of subjects enrolled
    Hungary: 20
    Worldwide total number of subjects
    106
    EEA total number of subjects
    49
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    58
    Adolescents (12-17 years)
    48
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study consisted of a Screening phase, a 4-week dose response phase (Phase 1), followed by a 4-week placebo controlled withdrawal phase (Phase 2).

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Enalapril
    Arm description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of enalapril based on their weight: low weight (≥20 to <50 kg) participants - starting dose 2.5 mg with optional titration to 5 and then 10 mg; mid weight (≥50 to <80 kg) participants - starting dose 5 mg with optional titration to 10 and then 20 mg; high weight (≥80 to ≤150 kg) participants - starting dose 10 mg with optional titration to 20 and then 40 mg.
    Arm type
    		 Off-therapy Extension Study

    Investigational medicinal product name
    Enalapril
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received one of the following doses based on their weight: Low weight (≥20 to <50 kg) patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight (≥50 to <80 kg) patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight (≥80 to ≤150 kg) patients: Starting dose 10 mg with optional titration to 20 and then 40 mg

    Arm title
    		 Aliskiren
    Arm description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of aliskiren based on their weight: low weight (≥20 to <50 kg) participants - starting dose 37.5 mg with optional titration to 75 and then 150 mg; mid weight (≥50 to <80 kg) participants - starting dose 75 mg with optional titration to 150 and then 300 mg; high weight (≥80 to ≤150 kg) participants - starting dose 150 mg with optional titration to 300 and then 600 mg.
    Arm type
    		 Off-therapy Extension Study

    Investigational medicinal product name
    Aliskiren
    Investigational medicinal product code
    Other name
    SPP100
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet) in a low, mid and high dose was dispensed in the previous studies [CSPP100A2365 and/or CSPP100A2365E1].

    Number of subjects in period 1
    		Enalapril Aliskiren
    Started
    51
    55
    Completed
    49
    50
    Not completed
    2
    5
         Consent withdrawn by subject
    1
    2
         Administrative problems
    1
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Enalapril
    Reporting group description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of enalapril based on their weight: low weight (≥20 to <50 kg) participants - starting dose 2.5 mg with optional titration to 5 and then 10 mg; mid weight (≥50 to <80 kg) participants - starting dose 5 mg with optional titration to 10 and then 20 mg; high weight (≥80 to ≤150 kg) participants - starting dose 10 mg with optional titration to 20 and then 40 mg.

    Reporting group title
    Aliskiren
    Reporting group description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of aliskiren based on their weight: low weight (≥20 to <50 kg) participants - starting dose 37.5 mg with optional titration to 75 and then 150 mg; mid weight (≥50 to <80 kg) participants - starting dose 75 mg with optional titration to 150 and then 300 mg; high weight (≥80 to ≤150 kg) participants - starting dose 150 mg with optional titration to 300 and then 600 mg.

    Reporting group values
    		 Enalapril Aliskiren Total
    Number of subjects
    		 51 55 106
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 28 30 58
        Adolescents (12-17 years)
    		 23 25 48
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 11.5 ± 3.32 11.4 ± 3.21 -
    Gender categorical
    Units: Subjects
        Female
    		 19 23 42
        Male
    		 32 32 64

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Enalapril
    Reporting group description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of enalapril based on their weight: low weight (≥20 to <50 kg) participants - starting dose 2.5 mg with optional titration to 5 and then 10 mg; mid weight (≥50 to <80 kg) participants - starting dose 5 mg with optional titration to 10 and then 20 mg; high weight (≥80 to ≤150 kg) participants - starting dose 10 mg with optional titration to 20 and then 40 mg.

    Reporting group title
    Aliskiren
    Reporting group description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of aliskiren based on their weight: low weight (≥20 to <50 kg) participants - starting dose 37.5 mg with optional titration to 75 and then 150 mg; mid weight (≥50 to <80 kg) participants - starting dose 75 mg with optional titration to 150 and then 300 mg; high weight (≥80 to ≤150 kg) participants - starting dose 150 mg with optional titration to 300 and then 600 mg.

    Primary: Change in Weight Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the Enrolled to Follow-up Set (EFS)

    		 Close Top of page
    End point title
    		 Change in Weight Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the Enrolled to Follow-up Set (EFS)
    End point description
    Participant weight was measured at Baseline (Visit 2 of the Core study), LT Visit 17, LT Visit 18 ([Week 104] only for participants identified in the core study as having primary hypertension), and LT Visit 19 ([Week 156] only for participants identified in the core study as having secondary hypertension). Body weight was measured to the nearest 0.1 kg in indoor clothing, but without shoes.
    End point type
    Primary
    End point timeframe
    Baseline to LT Visit 18 (Week 104): 2 years (104 weeks)
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    49 [1]
    50 [2]
    Units: kilogram(s)
        least squares mean (standard error)
    8.90 ± 1.359
    9.22 ± 1.399
    Notes
    [1] - Consisted of all participants who signed the informed consent form for the second extension study.
    [2] - Consisted of all participants who signed the informed consent form for the second extension study.
    Statistical analysis title
    		 Change in Weight Assessments
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.84 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.74
         upper limit
    		 3.37
    Notes
    [3] - Treatment regimen, region, age strata, and hypertension etiology (primary, secondary) as factors, and Baseline weight as covariates.
    [4] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.

    Primary: Change in Height Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS

    		 Close Top of page
    End point title
    		 Change in Height Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS
    End point description
    Participant height was measured at Baseline (Visit 2 of the Core study), LT Visit 17, LT Visit 18 ([Week 104] only for participants identified in the core study as having primary hypertension), and LT Visit 19 ([Week 156] only for participants identified in the core study as having secondary hypertension).
    End point type
    Primary
    End point timeframe
    Change in Height Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    49 [5]
    50 [6]
    Units: centimetre
        least squares mean (standard error)
    7.27 ± 0.586
    7.96 ± 0.607
    Notes
    [5] - Consisted of all participants who signed the informed consent form for the second extension study.
    [6] - Consisted of all participants who signed the informed consent form for the second extension study.
    Statistical analysis title
    		 Change in Height Assessments
    Statistical analysis description
    Treatment regimen, region, age strata, and hypertension etiology (primary, secondary) as factors, and Baseline height as covariates.
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.303 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.63
         upper limit
    		 2.02
    Notes
    [7] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.

    Primary: Change in BMI Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS

    		 Close Top of page
    End point title
    		 Change in BMI Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS
    End point description
    Participant height and weight was measured at Baseline (Visit 2 of the Core study), LT Visit 17, LT Visit 18 ([Week 104] only for participants identified in the core study as having primary hypertension), and LT Visit 19 ([Week 156] only for participants identified in the core study as having secondary hypertension). BMI was derived.
    End point type
    Primary
    End point timeframe
    Baseline to LT Visit 18 (Week 104): 2 years (104 weeks)
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    49 [8]
    50 [9]
    Units: kg/m^2
        least squares mean (standard error)
    1.53 ± 0.487
    1.56 ± 0.502
    Notes
    [8] - Consisted of all participants who signed the informed consent form for the second extension study.
    [9] - Consisted of all participants who signed the informed consent form for the second extension study.
    Statistical analysis title
    		 Change in BMI Assessments
    Statistical analysis description
    Treatment regimen, region, age strata, and hypertension etiology (primary, secondary) as factors, and Baseline BMI as covariates.
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.957 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.06
         upper limit
    		 1.12
    Notes
    [10] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.

    Primary: Change in Neurocognitive Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS

    		 Close Top of page
    End point title
    		 Change in Neurocognitive Assessments From Baseline (Visit 2 of the Core Study) to Long Term (LT) Visit 18 (Week 104) for the EFS [11]
    End point description
    All participants who were determined to have secondary hypertension in the core study and had a Baseline (Visit 2) standardized neurocognitive assessment in the core study received follow-up neurocognitive assessments at LT Visit 18 and LT Visit 19 with the same tool. The neurocognitive assessment of development included assessment of the following abilities: Attention, Processing speed, Working memory, and Motor speed. For Numbers (Forward and Backward Raw Score), Visual Matching (Number Correct), Sequences (Total Raw Score): positive change indicates a numerical increase, which is considered a better outcome/improvement; negative change/numerical decrease is considered a worse outcome/decline. For Visual Matching (Time to Complete), Time Tapping (Right and Left Hands), and Timed Gait: positive change indicates a numerical increase, which is considered a worse outcome/decline; negative change/numerical decrease is considered a better outcome/improvement.
    End point type
    Primary
    End point timeframe
    Baseline to LT Visit 18 (Week 104): 2 years (104 weeks)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were reported for this primary end point.
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    8 [12]
    6 [13]
    Units: Count of Participants
    number (not applicable)
        Numbers: Forward raw score - Positive change
    8
    4
        Numbers: Forward raw score - No change
    0
    1
        Numbers: Forward raw score - Negative change
    0
    1
        Numbers: Backward raw score - Positive change
    5
    4
        Numbers: Backward raw score - No change
    2
    1
        Numbers: Backward raw score - Negative change
    1
    1
        Visual matching: Number correct - Positive change
    7
    6
        Visual matching: Number correct - No change
    0
    0
        Visual matching: Number correct - Negative change
    1
    0
        Visual matching: Time to complete-sec - Pos change
    0
    0
        Visual matching: Time to complete-sec - No change
    7
    6
        Visual matching: Time to complete-sec - Neg change
    1
    0
        Sequences: Total raw score - Positive change
    6
    6
        Sequences: Total raw score - No change
    1
    0
        Sequences: Total raw score - Negative change
    1
    0
        Time tapping: Right hand - Positive change
    7
    3
        Time tapping: Right hand - No change
    0
    0
        Time tapping: Right hand - Negative change
    1
    3
        Time tapping: Left hand - Positive change
    4
    2
        Time tapping: Left hand - No change
    3
    2
        Time tapping: Left hand - Negative change
    1
    2
        Timed gait: Number of seconds- Positive change
    4
    3
        Timed gait: Number of seconds- No change
    3
    0
        Timed gait: Number of seconds- Negative change
    1
    2
    Notes
    [12] - Consisted of all participants who signed the informed consent form for the second extension study.
    [13] - Consisted of all participants who signed the informed consent form. Timed gait: Number of seconds =5
    No statistical analyses for this end point

    Secondary: Change in Weight Assessments From Baseline (Visit 2 of the Core Study) to End of Study (EOS) by Hypertension Group

    		 Close Top of page
    End point title
    		 Change in Weight Assessments From Baseline (Visit 2 of the Core Study) to End of Study (EOS) by Hypertension Group
    End point description
    Participant weight was measured at Baseline (Visit 2 of the Core study), LT Visit 17, LT Visit 18 ([Week 104] only for participants identified in the core study as having primary hypertension), and LT Visit 19 ([Week 156] only for participants identified in the core study as having secondary hypertension). Body weight was measured to the nearest 0.1 kg in indoor clothing, but without shoes.
    End point type
    Secondary
    End point timeframe
    Baseline to EOS (2 to 3 years). EOS was defined as LT Visit 18 (Week 104) and LT Visit 19 (Week 156) for participants with primary and secondary hypertension, respectively.
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    41 [14]
    44 [15]
    Units: kilogram(s)
    least squares mean (standard error)
        Primary Hypertension Group
    8.31 ± 1.195
    8.33 ± 1.182
        Secondary Hypertension Group
    -0.73 ± 3.699
    -3.80 ± 3.445
    Notes
    [14] - Consisted of all participants who signed the ICF for the second extension study. N= 41, 8
    [15] - Consisted of all participants who signed the ICF for the second extension study. N= 44, 7
    Statistical analysis title
    		 Change in Weight Assessments - Primary
    Statistical analysis description
    Primary Hypertension group (at LT Visit 18 [Week 104]) Treatment regimen, region, age strata, and Baseline weight as covariates
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.992 [16]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.29
         upper limit
    		 3.33
    Notes
    [16] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.
    Statistical analysis title
    		 Change in Weight Assessments - Secondary
    Statistical analysis description
    Secondary hypertension group (at LT Visit 19 [Week 156]) Treatment regimen, region, age strata, and Baseline weight as covariates.
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.215 [17]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.22
         upper limit
    		 2.1
    Notes
    [17] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.

    Secondary: Change in Height Assessments From Baseline (Visit 2 of the Core Study) to EOS by Hypertension Group

    		 Close Top of page
    End point title
    		 Change in Height Assessments From Baseline (Visit 2 of the Core Study) to EOS by Hypertension Group
    End point description
    Participant height was measured at Baseline (Visit 2 of the Core study), LT Visit 17, LT Visit 18 ([Week 104] only for participants identified in the core study as having primary hypertension), and LT Visit 19 ([Week 156] only for participants identified in the core study as having secondary hypertension).
    End point type
    Secondary
    End point timeframe
    Baseline to EOS (2 to 3 years). EOS was defined as LT Visit 18 (Week 104) and LT Visit 19 (Week 156) for participants with primary and secondary hypertension, respectively.
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    41 [18]
    44 [19]
    Units: centimetre
    least squares mean (standard error)
        Primary Hypertension Group
    6.80 ± 0.529
    7.42 ± 0.528
        Secondary Hypertension Group
    16.05 ± 3.316
    16.96 ± 3.044
    Notes
    [18] - Consisted of all participants who signed the ICF for the second extension study. N= 41, 8
    [19] - Consisted of all participants who signed the ICF for the second extension study. N= 44, 7
    Statistical analysis title
    		 Change in Height Assessments - Primary
    Statistical analysis description
    Primary Hypertension group (at LT Visit 18 [Week 104]) Treatment regimen, region, age strata, and Baseline height as covariates
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.403 [20]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.85
         upper limit
    		 2.09
    Notes
    [20] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.
    Statistical analysis title
    		 Change in Height Assessments - Secondary
    Statistical analysis description
    Secondary hypertension group (at LT Visit 19 [Week 156])
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.67 [21]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.74
         upper limit
    		 5.57
    Notes
    [21] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.

    Secondary: Change in BMI Assessments From Baseline (Visit 2 of the Core Study) to EOS by Hypertension Group

    		 Close Top of page
    End point title
    		 Change in BMI Assessments From Baseline (Visit 2 of the Core Study) to EOS by Hypertension Group
    End point description
    Participant weight and height was measured at Baseline (Visit 2 of the Core study), LT Visit 17, LT Visit 18 ([Week 104] only for participants identified in the core study as having primary hypertension), and LT Visit 19 ([Week 156] only for participants identified in the core study as having secondary hypertension). Body weight was measured to the nearest 0.1 kg in indoor clothing, but without shoes. BMI was derived.
    End point type
    Secondary
    End point timeframe
    Baseline to EOS (2 to 3 years). EOS was defined as LT Visit 18 (Week 104) and LT Visit 19 (Week 156) for participants with primary and secondary hypertension, respectively.
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    41 [22]
    44 [23]
    Units: kg/m^2
    least squares mean (standard error)
        Primary Hypertension Group
    1.30 ± 0.428
    1.19 ± 0.424
        Secondary Hypertension Group
    -1.81 ± 1.336
    -2.97 ± 1.397
    Notes
    [22] - Consisted of all participants who signed the ICF for the second extension study. N= 41, 8
    [23] - Consisted of all participants who signed the ICF for the second extension study. N= 44, 7
    Statistical analysis title
    		 Change in BMI Assessments - Primary
    Statistical analysis description
    Primary Hypertension group (at LT Visit 18 [Week 104]) Treatment regimen, region, age strata, and Baseline BMI as covariates
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.86 [24]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.29
         upper limit
    		 1.08
    Notes
    [24] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.
    Statistical analysis title
    		 Change in BMI Assessments - Secondary
    Statistical analysis description
    Secondary hypertension group (at LT Visit 19 [Week 156]) Treatment regimen, region, age strata, and Baseline BMI as covariates.
    Comparison groups
    Enalapril v Aliskiren
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.32 [25]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.66
         upper limit
    		 1.32
    Notes
    [25] - p-value for statistical significance at 0.05 level for 2-sided superiority testing.

    Secondary: Change in Neurocognitive Assessments From Baseline (Visit 2 of the Core Study) to EOS by Hypertension Group

    		 Close Top of page
    End point title
    		 Change in Neurocognitive Assessments From Baseline (Visit 2 of the Core Study) to EOS by Hypertension Group
    End point description
    All participants who were determined to have secondary hypertension in the core study and had a Baseline (Visit 2) standardized neurocognitive assessment in the core study received follow-up neurocognitive assessments at LT Visit 18 and LT Visit 19 with the same tool. The neurocognitive assessment of development included assessment of the following abilities: Attention, Processing speed, Working memory, and Motor speed. For Numbers (Forward and Backward Raw Score), Visual Matching (Number Correct), Sequences (Total Raw Score): positive change indicates a numerical increase, which is considered a better outcome/improvement; negative change/numerical decrease is considered a worse outcome/decline. For Visual Matching (Time to Complete), Time Tapping (Right and Left Hands), and Timed Gait: positive change indicates a numerical increase, which is considered a worse outcome/decline; negative change/numerical decrease is considered a better outcome/improvement.
    End point type
    Secondary
    End point timeframe
    Baseline to EOS (3 years). EOS was defined as LT Visit 19 (Week 156) for participants with secondary hypertension.
    End point values
    		 Enalapril Aliskiren
    Number of subjects analysed
    8 [26]
    6 [27]
    Units: participants
    number (not applicable)
        Numbers: Forward raw score: Positive change
    7
    5
        Numbers: Forward raw score: No change
    1
    0
        Numbers: Forward raw score: Negative change
    0
    1
        Numbers: Backward raw score: Positive change
    5
    4
        Numbers: Backward raw score: No change
    2
    1
        Numbers: Backward raw score: Negative change
    1
    1
        Visual matching: Number correct: Positive change
    6
    6
        Visual matching: Number correct: No change
    0
    0
        Visual matching: Number correct: Negative change
    2
    0
        Visual matching: Time to complete: Positive change
    0
    0
        Visual matching: Time to complete: No change
    7
    6
        Visual matching: Time to complete: Negative change
    1
    0
        Sequences: Total raw score: Positive change
    8
    6
        Sequences: Total raw score: No change
    0
    0
        Sequences: Total raw score: Negative change
    0
    0
        Time tapping: Right hand: Positive change
    5
    1.076
        Time tapping: Right hand: No change
    2
    1
        Time tapping: Right hand: Negative change
    1
    4
        Time tapping: Left hand: Positive change
    2
    2
        Time tapping: Left hand: No change
    3
    1
        Time tapping: Left hand: Negative change
    3
    3
        Timed gait: Number of seconds: Positive change
    4
    3
        Timed gait: Number of seconds: No change
    2
    0
        Timed gait: Number of seconds: Negative change
    2
    3
    Notes
    [26] - The EFS consisted of all participants who signed the ICF for the second extension study.
    [27] - The EFS consisted of all participants who signed the ICF for the second extension study.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    This study only collected the occurrence of Serious Adverse Events (SAEs) occurring within the first 30 days after the participant had completed the first extension study. SAEs experienced after this 30 day period were reported to Novartis/Noden.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Enalapril
    Reporting group description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of enalapril based on their weight: low weight (≥20 to <50 kg) participants - starting dose 2.5 mg with optional titration to 5 and then 10 mg; mid weight (≥50 to <80 kg) participants - starting dose 5 mg with optional titration to 10 and then 20 mg; high weight (≥80 to ≤150 kg) participants - starting dose 10 mg with optional titration to 20 and then 40 mg.

    Reporting group title
    Aliskiren
    Reporting group description
    		 No study treatment (aliskiren or enalapril) was administered in this off-therapy non-interventional second extension study. The arm/group in this second extension study refers to the actual treatment arm/group assigned at the end of the first extension study (Study CSPP100A2365E1: ClinicalTrials.gov Identifier: NCT01151410). During Study CSPP100A2365E1, participants were to receive one of the following doses of aliskiren based on their weight: low weight (≥20 to <50 kg) participants - starting dose 37.5 mg with optional titration to 75 and then 150 mg; mid weight (≥50 to <80 kg) participants - starting dose 75 mg with optional titration to 150 and then 300 mg; high weight (≥80 to ≤150 kg) participants - starting dose 150 mg with optional titration to 300 and then 600 mg.

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: There were no non-serious adverse events reported in this study.
    Serious adverse events
    		 Enalapril Aliskiren
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 55 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Congenital, familial and genetic disorders
    Phimosis
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Enalapril Aliskiren
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 55 (0.00%)

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to small sample sizes in the secondary hypertension etiology subgroups, the corresponding p-values for treatment comparisons should be interpreted with caution.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 07 16:18:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA