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    Clinical Trial Results:
    A Phase III, Randomized, Open-Label, Parallel-Group, Dose-Ranging Clinical Trial to Study the Safety and Efficacy of MK-0954/Losartan Potassium in Pediatric Patients With Hypertension

    Summary
    EudraCT number
    		 2008-004732-20
    Trial protocol
    		 HU   LT   GB   ES   Outside EU/EEA  
    Global end of trial date
    14 Aug 2012

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Mar 2016
    First version publication date
    15 Jul 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    0954-337
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00756938
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDiscosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDiscosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000008-PIP01-07
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Aug 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Aug 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    (1) To define a dose-response relationship for losartan in hypertensive children aged 6 months to 6 years, after a 21-day open-label treatment period (response assessed by change from baseline in mean trough systolic blood pressure [SBP]). (2) To investigate the safety and tolerability of losartan at doses up to 1.4 mg/kg/day in hypertensive children aged 6 months to 6 years after 12 weeks of treatment.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jun 2008
    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
    Norway: 1
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Lithuania: 15
    Country: Number of subjects enrolled
    Chile: 3
    Country: Number of subjects enrolled
    India: 8
    Country: Number of subjects enrolled
    Philippines: 10
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Colombia: 2
    Country: Number of subjects enrolled
    Guatemala: 22
    Country: Number of subjects enrolled
    Brazil: 24
    Country: Number of subjects enrolled
    United States: 7
    Worldwide total number of subjects
    101
    EEA total number of subjects
    22
    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)
    27
    Children (2-11 years)
    74
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants met 1 of the following: 6 months to < 1 year old - mean SBP ≥ 95th percentile ; ≥ 1 year old -mean systolic and/or diastolic blood pressure (DBP) ≥ 95th percentile; had co-morbidities with: mean SBP ≥ 90th percentile (6 months to < 1 year old) or mean SBP and/or DBP ≥ 90th percentile (≥ 1 year old).

    Period 1
    Period 1 title
    12-week Base Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan potassium 0.1 to 1.4 mg/kg
    Arm description
    		 Open-label losartan at starting dose of 0.1 mg/kg/day with uptitration at Weeks 3, 6 or 9 to the next highest dose level if blood pressure goal not achieved
    Arm type
    		 Experimental

    Investigational medicinal product name
    losartan potassium
    Investigational medicinal product code
    Other name
    MK-0954, Cozaar®
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    losartan potassium, dry powder, to be suspended in liquid and given orally, once daily; doses will start at 0.1 mg/kg and can be escalated up to 1.4 mg/kg (maximum dose 100 mg) until target blood pressure is reached.

    Arm title
    		 Losartan potassium 0.3 to 1.4 mg/kg
    Arm description
    		 Open-label losartan at starting dose of 0.3 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved.
    Arm type
    		 Experimental

    Investigational medicinal product name
    losartan potassium
    Investigational medicinal product code
    Other name
    MK-0954, Cozaar®
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    losartan potassium, dry powder, to be suspended in liquid and given orally, once daily; doses will start at 0.3 mg/kg and can be escalated up to 1.4 mg/kg (maximum dose 100 mg) until target blood pressure is reached.

    Arm title
    		 Losartan potassium 0.7 to 1.4 mg/kg
    Arm description
    		 Open-label losartan at starting dose of 0.7 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved
    Arm type
    		 Experimental

    Investigational medicinal product name
    losartan potassium
    Investigational medicinal product code
    Other name
    MK-0954, Cozaar®
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    losartan potassium, dry powder, to be suspended in liquid and given orally, once daily; doses will start at 0.7 mg/kg and can be escalated up to 1.4 mg/kg (maximum dose 100 mg) until target blood pressure is reached.

    Number of subjects in period 1
    		Losartan potassium 0.1 to 1.4 mg/kg Losartan potassium 0.3 to 1.4 mg/kg Losartan potassium 0.7 to 1.4 mg/kg
    Started
    33
    34
    34
    Completed
    31
    34
    32
    Not completed
    2
    0
    2
         Protocol-specific Criteria Met
    1
    -
    1
         Lost to follow-up
    1
    -
    -
         Protocol deviation
    -
    -
    1
    Period 2
    Period 2 title
    Extension
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Losartan potassium-Extension
    Arm description
    		 Participants who elected to enter extension; dose level of Losartan was that which was being administered at end of base study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    losartan potassium
    Investigational medicinal product code
    Other name
    MK-0954, Cozaar®
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    losartan potassium, dry powder, to be suspended in liquid and given orally, once daily; doses will start at 0.1 mg/kg, 0.3 mg/kg, and 0.7 mg/kg, respectively, in the three study arms and can be escalated up to 1.4 mg/kg (maximum dose 100 mg) until target blood pressure is reached.

    Number of subjects in period 2 [1]
    		Losartan potassium-Extension
    Started
    90
    Completed
    53
    Not completed
    37
         Physician decision
    3
         Consent withdrawn by subject
    10
         End of Study
    11
         Adverse event, non-fatal
    1
         Protocol-specific Criteria Met
    9
         Lost to follow-up
    1
         Lack of efficacy
    1
         Protocol deviation
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all participants who completed the base study elected to enter extension study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Losartan potassium 0.1 to 1.4 mg/kg
    Reporting group description
    		 Open-label losartan at starting dose of 0.1 mg/kg/day with uptitration at Weeks 3, 6 or 9 to the next highest dose level if blood pressure goal not achieved

    Reporting group title
    Losartan potassium 0.3 to 1.4 mg/kg
    Reporting group description
    		 Open-label losartan at starting dose of 0.3 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved.

    Reporting group title
    Losartan potassium 0.7 to 1.4 mg/kg
    Reporting group description
    		 Open-label losartan at starting dose of 0.7 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved

    Reporting group values
    		 Losartan potassium 0.1 to 1.4 mg/kg Losartan potassium 0.3 to 1.4 mg/kg Losartan potassium 0.7 to 1.4 mg/kg Total
    Number of subjects
    		 33 34 34 101
    Age categorical
    Units: Subjects
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 40.2 ( 24.4 ) 45 ( 21.5 ) 40.6 ( 21.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 13 16 14 43
        Male
    		 20 18 20 58

    End points

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    End points reporting groups
    Reporting group title
    Losartan potassium 0.1 to 1.4 mg/kg
    Reporting group description
    		 Open-label losartan at starting dose of 0.1 mg/kg/day with uptitration at Weeks 3, 6 or 9 to the next highest dose level if blood pressure goal not achieved

    Reporting group title
    Losartan potassium 0.3 to 1.4 mg/kg
    Reporting group description
    		 Open-label losartan at starting dose of 0.3 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved.

    Reporting group title
    Losartan potassium 0.7 to 1.4 mg/kg
    Reporting group description
    		 Open-label losartan at starting dose of 0.7 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved
    Reporting group title
    Losartan potassium-Extension
    Reporting group description
    		 Participants who elected to enter extension; dose level of Losartan was that which was being administered at end of base study.

    Subject analysis set title
    Base Study-Losartan potassium 0.1 mg/kg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.

    Subject analysis set title
    Base Study-Losartan potassium 0.3 mg/kg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.

    Subject analysis set title
    Base Study-Losartan potassium 0.7 mg/kg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.

    Subject analysis set title
    Base Study-Losartan potassium 1.4 mg/kg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.

    Subject analysis set title
    Extension-Losartan potassium
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.

    Primary: Mean Change from Baseline in Systolic Blood Pressure (SBP)

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    End point title
    		 Mean Change from Baseline in Systolic Blood Pressure (SBP)
    End point description
    Sitting blood pressure ([BP] or supine if child could not sit) was measured after the participant had been seated for 5 minutes with back supported, feet on the floor and right arm (or left arm if it was the customary side for BP measurement for the participant) supported at heart level. Systolic BP was determined by averaging 3 replicate measurements obtained at least 1 minute apart.
    End point type
    Primary
    End point timeframe
    Baseline and Day 21
    End point values
    		 Losartan potassium 0.1 to 1.4 mg/kg Losartan potassium 0.3 to 1.4 mg/kg Losartan potassium 0.7 to 1.4 mg/kg
    Number of subjects analysed
    32
    34
    33
    Units: mmHg
        arithmetic mean (standard deviation)
    -7.31 ( 12.53 )
    -7.65 ( 7.49 )
    -6.67 ( 7.86 )
    Statistical analysis title
    		 Comparsion of Change from Baseline
    Statistical analysis description
    The slope of change in SBP after 21 days treatment as compared to baseline as a function of dose was assessed using an analysis of covariance (ANCOVA) model with terms for dose (as a continuous covariate: 0.1, 0.3 or 0.7 mg/kg/day), weight (as a continuous covariate) and presence of co-morbidities/end organ damage (yes/no). The primary hypothesis was assessed by testing whether the slope for dose in the above regression model was zero or not.
    Comparison groups
    Losartan potassium 0.3 to 1.4 mg/kg v Losartan potassium 0.7 to 1.4 mg/kg v Losartan potassium 0.1 to 1.4 mg/kg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.753
    Method
    		 ANCOVA
    Parameter type
    		 Slope
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.45
         upper limit
    		 8.9

    Primary: Number of Participants Who Reported 1 or more Clinical and/or Laboratory Adverse Event(s)

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    End point title
    		 Number of Participants Who Reported 1 or more Clinical and/or Laboratory Adverse Event(s) [1]
    End point description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE.
    End point type
    Primary
    End point timeframe
    up to 12 weeks (Base Study); up to 24 months (Extension)
    Notes
    [1] - 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 was planned for this endpoint.
    End point values
    		 Base Study-Losartan potassium 0.1 mg/kg Base Study-Losartan potassium 0.3 mg/kg Base Study-Losartan potassium 0.7 mg/kg Base Study-Losartan potassium 1.4 mg/kg Extension-Losartan potassium
    Number of subjects analysed
    34
    54
    63
    33
    90
    Units: Participants
        Clinical Adverse Event
    21
    30
    36
    22
    75
        Laboratory Adverse Event
    1
    1
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event

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    End point title
    		 Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event [2]
    End point description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The number of participants who were discontinued from the study due to an AE regardless of relatedness to the study drug were recorded.
    End point type
    Primary
    End point timeframe
    up to 12 weeks (Base Study); up to 24 months (Extension)
    Notes
    [2] - 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 was planned for this endpoint.
    End point values
    		 Base Study-Losartan potassium 0.1 mg/kg Base Study-Losartan potassium 0.3 mg/kg Base Study-Losartan potassium 0.7 mg/kg Base Study-Losartan potassium 1.4 mg/kg Extension-Losartan potassium
    Number of subjects analysed
    34
    54
    63
    33
    90
    Units: Participants
        Clinical Adverse Events
    0
    0
    0
    0
    1
        Laboratory Adverse Events
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Mean Change from Baseline in Diastolic Blood Pressure

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    End point title
    		 Mean Change from Baseline in Diastolic Blood Pressure
    End point description
    Sitting BP (or supine if child could not sit) was measured after the participant had been seated for 5 minutes with back supported, feet on the floor and right arm (or left arm if it was the customary side for BP measurement for the patient) supported at heart level. Diastolic BP was determined by averaging 3 replicate measurements obtained at least 1 minute apart.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 21
    End point values
    		 Losartan potassium 0.1 to 1.4 mg/kg Losartan potassium 0.3 to 1.4 mg/kg Losartan potassium 0.7 to 1.4 mg/kg
    Number of subjects analysed
    32
    34
    33
    Units: mmHg
        arithmetic mean (standard deviation)
    -8.25 ( 11.76 )
    -5.15 ( 8.06 )
    -6.73 ( 8.59 )
    Statistical analysis title
    		 Comparison of Change from Baseline
    Statistical analysis description
    The slope of change in DBP after 21 days treatment as compared to baseline as a function of dose was assessed using an analysis of covariance (ANCOVA) model with terms for dose (as a continuous covariate: 0.1, 0.3 or 0.7 mg/kg/day), weight (as a continuous covariate) and presence of co-morbidities/end organ damage (yes/no). The primary hypothesis was assessed by testing whether the slope for dose in the above regression model was zero or not.
    Comparison groups
    Losartan potassium 0.1 to 1.4 mg/kg v Losartan potassium 0.3 to 1.4 mg/kg v Losartan potassium 0.7 to 1.4 mg/kg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.643
    Method
    		 ANCOVA
    Parameter type
    		 Slope
    Point estimate
    1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.9
         upper limit
    		 9.51

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    up to 12 weeks (Base Study); up to 24 months (Extension)
    Adverse event reporting additional description
    All randomized participants who received at least 1 dose of study drug. Adverse events are reported by the dose taken at the time of the event and not the study group to which they were randomized. A participant may have reported an adverse event when taking different dose levels and therefore may have been counted more than once.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Base Study-Losartan potassium 0.1 mg/kg
    Reporting group description
    		 Participants who received 0.1 mg/kg losartan during base study.

    Reporting group title
    Base Study-Losartan potassium 0.3 mg/kg
    Reporting group description
    		 Participants who received 0.3 mg/kg losartan during base study

    Reporting group title
    Base Study-Losartan potassium 0.7 mg/kg
    Reporting group description
    		 Participants who received 0.7 mg/kg losartan during base study

    Reporting group title
    Base Study-Losartan potassium 1.4 mg/kg
    Reporting group description
    		 Participants who received 1.4 mg/kg losartan during base study.

    Reporting group title
    Extension Study-Losartan potassium 0.1 mg/kg
    Reporting group description
    		 Participants who received 0.1 mg/kg losartan during extension study

    Reporting group title
    Extension Study-Losartan potassium 0.3 mg/kg
    Reporting group description
    		 Participants who received 0.3 mg/kg losartan during extension study

    Reporting group title
    Extension Study-Losartan potassium 0.7 mg/kg
    Reporting group description
    		 Participants who received 0.7 mg/kg losartan during extension study

    Reporting group title
    Extension Study-Losartan potassium 1.4 mg/kg
    Reporting group description
    		 Participants who received 1.4 mg/kg losartan during extension study

    Serious adverse events
    		 Base Study-Losartan potassium 0.1 mg/kg Base Study-Losartan potassium 0.3 mg/kg Base Study-Losartan potassium 0.7 mg/kg Base Study-Losartan potassium 1.4 mg/kg Extension Study-Losartan potassium 0.1 mg/kg Extension Study-Losartan potassium 0.3 mg/kg Extension Study-Losartan potassium 0.7 mg/kg Extension Study-Losartan potassium 1.4 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 34 (8.82%)
    2 / 54 (3.70%)
    2 / 63 (3.17%)
    0 / 33 (0.00%)
    3 / 15 (20.00%)
    5 / 28 (17.86%)
    2 / 31 (6.45%)
    5 / 42 (11.90%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Nephroblastoma
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Thermal burn
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychomotor retardation
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Adenoiditis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis bacterial
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    2 / 28 (7.14%)
    1 / 31 (3.23%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 54 (0.00%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salmonellosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    1 / 31 (3.23%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Base Study-Losartan potassium 0.1 mg/kg Base Study-Losartan potassium 0.3 mg/kg Base Study-Losartan potassium 0.7 mg/kg Base Study-Losartan potassium 1.4 mg/kg Extension Study-Losartan potassium 0.1 mg/kg Extension Study-Losartan potassium 0.3 mg/kg Extension Study-Losartan potassium 0.7 mg/kg Extension Study-Losartan potassium 1.4 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 34 (47.06%)
    26 / 54 (48.15%)
    26 / 63 (41.27%)
    20 / 33 (60.61%)
    12 / 15 (80.00%)
    20 / 28 (71.43%)
    20 / 31 (64.52%)
    28 / 42 (66.67%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lip and/or oral cavity cancer stage III
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    3 / 34 (8.82%)
    4 / 54 (7.41%)
    3 / 63 (4.76%)
    1 / 33 (3.03%)
    1 / 15 (6.67%)
    4 / 28 (14.29%)
    2 / 31 (6.45%)
    4 / 42 (9.52%)
         occurrences all number
    3
    6
    3
    1
    1
    5
    2
    10
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 54 (3.70%)
    2 / 63 (3.17%)
    5 / 33 (15.15%)
    1 / 15 (6.67%)
    1 / 28 (3.57%)
    3 / 31 (9.68%)
    5 / 42 (11.90%)
         occurrences all number
    2
    3
    2
    5
    1
    1
    3
    9
    Rhinitis allergic
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    1 / 63 (1.59%)
    1 / 33 (3.03%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    Investigations
    Protein urine present
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    2 / 31 (6.45%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    1
    Red blood cell count decreased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    2 / 31 (6.45%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Urine leukocyte esterase positive
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    2 / 31 (6.45%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    2
    0
    White blood cells urine positive
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    2 / 31 (6.45%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    2 / 28 (7.14%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    1
    0
    Ligament rupture
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    1 / 63 (1.59%)
    1 / 33 (3.03%)
    0 / 15 (0.00%)
    3 / 28 (10.71%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    1
    1
    0
    3
    0
    1
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 54 (3.70%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    2 / 15 (13.33%)
    0 / 28 (0.00%)
    2 / 31 (6.45%)
    1 / 42 (2.38%)
         occurrences all number
    0
    2
    1
    0
    2
    0
    2
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    1 / 28 (3.57%)
    1 / 31 (3.23%)
    1 / 42 (2.38%)
         occurrences all number
    2
    1
    0
    0
    1
    1
    1
    1
    Constipation
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    2 / 34 (5.88%)
    3 / 54 (5.56%)
    4 / 63 (6.35%)
    2 / 33 (6.06%)
    3 / 15 (20.00%)
    3 / 28 (10.71%)
    5 / 31 (16.13%)
    6 / 42 (14.29%)
         occurrences all number
    2
    3
    4
    2
    4
    5
    5
    8
    Vomiting
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 54 (1.85%)
    1 / 63 (1.59%)
    1 / 33 (3.03%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    2 / 31 (6.45%)
    3 / 42 (7.14%)
         occurrences all number
    1
    1
    1
    1
    0
    7
    2
    3
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 54 (3.70%)
    1 / 63 (1.59%)
    2 / 33 (6.06%)
    2 / 15 (13.33%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    4 / 42 (9.52%)
         occurrences all number
    0
    2
    1
    5
    2
    1
    0
    4
    Renal and urinary disorders
    Enuresis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Nephrocalcinosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Acute tonsillitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    2 / 15 (13.33%)
    1 / 28 (3.57%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 54 (3.70%)
    0 / 63 (0.00%)
    1 / 33 (3.03%)
    0 / 15 (0.00%)
    2 / 28 (7.14%)
    0 / 31 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    2
    0
    1
    0
    3
    0
    2
    Ear infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 54 (0.00%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    1 / 31 (3.23%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    1
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    Gastroenteritis viral
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    2 / 28 (7.14%)
    0 / 31 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    0
    Impetigo
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    2 / 31 (6.45%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    Laryngitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 34 (5.88%)
    7 / 54 (12.96%)
    3 / 63 (4.76%)
    2 / 33 (6.06%)
    2 / 15 (13.33%)
    4 / 28 (14.29%)
    5 / 31 (16.13%)
    2 / 42 (4.76%)
         occurrences all number
    2
    7
    3
    3
    3
    6
    6
    2
    Oral herpes
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    0 / 28 (0.00%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Otitis media acute
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 54 (1.85%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    1 / 28 (3.57%)
    2 / 31 (6.45%)
    2 / 42 (4.76%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    2
    3
    Pharyngitis
         subjects affected / exposed
    3 / 34 (8.82%)
    2 / 54 (3.70%)
    1 / 63 (1.59%)
    1 / 33 (3.03%)
    4 / 15 (26.67%)
    1 / 28 (3.57%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    3
    2
    1
    1
    5
    1
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 54 (1.85%)
    5 / 63 (7.94%)
    3 / 33 (9.09%)
    2 / 15 (13.33%)
    3 / 28 (10.71%)
    3 / 31 (9.68%)
    5 / 42 (11.90%)
         occurrences all number
    2
    1
    6
    3
    2
    3
    6
    13
    Rhinitis
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 54 (5.56%)
    0 / 63 (0.00%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    1 / 31 (3.23%)
    0 / 42 (0.00%)
         occurrences all number
    2
    3
    0
    0
    0
    4
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    1 / 63 (1.59%)
    0 / 33 (0.00%)
    0 / 15 (0.00%)
    0 / 28 (0.00%)
    2 / 31 (6.45%)
    5 / 42 (11.90%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    2
    6
    Tonsillitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    1 / 33 (3.03%)
    2 / 15 (13.33%)
    1 / 28 (3.57%)
    1 / 31 (3.23%)
    2 / 42 (4.76%)
         occurrences all number
    1
    0
    0
    1
    2
    2
    1
    2
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 54 (5.56%)
    2 / 63 (3.17%)
    0 / 33 (0.00%)
    1 / 15 (6.67%)
    4 / 28 (14.29%)
    3 / 31 (9.68%)
    4 / 42 (9.52%)
         occurrences all number
    1
    3
    3
    0
    1
    4
    8
    4
    Urinary tract infection
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 54 (3.70%)
    4 / 63 (6.35%)
    4 / 33 (12.12%)
    0 / 15 (0.00%)
    1 / 28 (3.57%)
    3 / 31 (9.68%)
    7 / 42 (16.67%)
         occurrences all number
    3
    2
    4
    4
    0
    1
    12
    13
    Viral infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 54 (0.00%)
    0 / 63 (0.00%)
    1 / 33 (3.03%)
    0 / 15 (0.00%)
    2 / 28 (7.14%)
    0 / 31 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Mar 2009
    AM1: The primary reason for protocol amendment 337-01 was to remove the COZAAR™ (losartan potassium) Worldwide Product Circular and replace with the COZAAR® (losartan potassium) United States Product Circular
    17 Jun 2010
    AM2: The primary reason for protocol amendment was to add language clarifying that Visit 1 screening procedures could be completed over more than 1 day if needed.
    20 May 2011
    AM3: The primary reason for protocol amendment was to clarify the duration of follow-up in the open-label extension.
    21 Mar 2012
    AM5: The primary reason for protocol amendment was to revert the lower age limit for inclusion into the study from 3 months to 6 months of age. The eligibility of children as young as 3 months was proposed in protocol amendment 337-04 but was not implemented due to regulatory concerns.

    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.
    None reported
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    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.

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