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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39361   clinical trials with a EudraCT protocol, of which   6446   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).
     
    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:
    Dose-ranging Study to Evaluate the Safety and Efficacy of Olmesartan Medoxomil in Children and Adolescents With Hypertension

    Summary
    EudraCT number
    2015-003329-32
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    15 Sep 2008

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Nov 2018
    First version publication date
    25 Nov 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    CS0866-A-U301
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00151775
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Daiichi Sankyo Pharma Development
    Sponsor organisation address
    399 Thornall Street, Edison, New Jersey, United States, 08837
    Public contact
    Clinical Trial Information, Daiichi Sankyo Development Ltd, +44 1753482800, euregaffairs@dsd-eu.com
    Scientific contact
    Clinical Trial Information, Daiichi Sankyo Development Ltd, +44 1753482800, euregaffairs@dsd-eu.com
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Sep 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Sep 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to evaluate the efficacy and safety of Olmesartan Medoxomil in subjects 6 to 16 years of age with high Blood Pressure or hypertension.
    Protection of trial subjects
    Subjects safety was assessed throughout the study by monitoring of adverse events (AEs) and routine laboratory safety tests, vital signs, and physical examination findings.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    27 Apr 2005
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    South Africa: 82
    Country: Number of subjects enrolled
    Uganda: 8
    Country: Number of subjects enrolled
    United States: 162
    Country: Number of subjects enrolled
    Zambia: 5
    Country: Number of subjects enrolled
    Argentina: 34
    Country: Number of subjects enrolled
    Chile: 7
    Country: Number of subjects enrolled
    Colombia: 19
    Country: Number of subjects enrolled
    Costa Rica: 6
    Country: Number of subjects enrolled
    India: 37
    Country: Number of subjects enrolled
    Kenya: 2
    Worldwide total number of subjects
    362
    EEA total number of subjects
    0
    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)
    9
    Children (2-11 years)
    158
    Adolescents (12-17 years)
    195
    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
    A total of 362 patients between 1 and 16 years of age were recruited on a global basis between 27 April 2005 and 15 September 2008.

    Period 1
    Period 1 title
    Period 1: Screening
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    All Patients
    Arm description
    Period 1 was a screening, wash-out period of approximately two weeks. All participants were included in the screening, wash-out period and during this period no intervention was administered.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    All Patients
    Started
    362
    Completed
    362
    Period 2
    Period 2 title
    Period 2: Double-blind, Dose Response
    Is this the baseline period?
    Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort A: High Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a high dose of olmesartan medoxomil suspension (OM), depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a high dose of olmesartan medoxomil, 20 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort A: Low Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a low dose of olmesartan medoxomil, 2.5 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort B: High Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a high dose of olmesartan medoxomil, 20 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort B: Low Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a low dose of olmesartan medoxomil, 2.5 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort C: OM in Periods 2, 3, and 4
    Arm description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received olmesartan medoxomil suspension (OM), 0.3 mg/kg orally once daily for 3 weeks.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: Period 1 is not the baseline period because it was a screening and wash-out period before randomization, so all subjects were included.
    Number of subjects in period 2
    Cohort A: High Dose OM in Periods 2 and 3 Cohort A: Low Dose OM in Periods 2 and 3 Cohort B: High Dose OM in Periods 2 and 3 Cohort B: Low Dose OM in Periods 2 and 3 Cohort C: OM in Periods 2, 3, and 4
    Started
    95
    95
    56
    56
    60
    Completed
    93
    89
    54
    53
    59
    Not completed
    2
    6
    2
    3
    1
         Protocol deviation
    -
    4
    1
    -
    -
         Physician decision
    -
    -
    1
    -
    -
         Unknown
    -
    -
    -
    1
    -
         Adverse event, non-fatal
    1
    2
    -
    -
    -
         Blood pressure goal was met
    -
    -
    -
    1
    -
         Lost to follow-up
    1
    -
    -
    1
    1
    Period 3
    Period 3 title
    Period 3: Double-blind, Withdrawal
    Is this the baseline period?
    No
    Allocation method
    Non-randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort A: High Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a high dose of olmesartan medoxomil suspension (OM), depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a high dose of olmesartan medoxomil, 20 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort A: Low Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a low dose of olmesartan medoxomil, 2.5 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort B: High Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a high dose of olmesartan medoxomil, 20 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort B: Low Dose OM in Periods 2 and 3
    Arm description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received a low dose of olmesartan medoxomil, 2.5 mg orally once daily for patients weighing more than 20 kg and less than 35 kg, and 40 mg once daily for patients weighing 35 kg or more.

    Arm title
    Cohort C: OM in Periods 2, 3, and 4
    Arm description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received olmesartan medoxomil suspension (OM), 0.3 mg/kg orally once daily for 3 weeks.

    Arm title
    Cohort A: Placebo in Period 3 (From High Dose in Period 2)
    Arm description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black participants) given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous high dose of OM.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received placebo orally once daily.

    Arm title
    Cohort A: Placebo in Period 3 (From Low Dose in Period 2)
    Arm description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous low dose of OM.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received placebo orally once daily.

    Arm title
    Cohort B: Placebo in Period 3 (From High Dose in Period 2)
    Arm description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black patients), given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous high dose of OM.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received placebo orally once daily.

    Arm title
    Cohort B: Placebo in Period 3 (From Low Dose in Period 2)
    Arm description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black patients), given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous low dose of OM.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received placebo orally once daily.

    Arm title
    Cohort C: Placebo in Period 3 (From OM in Period 2)
    Arm description
    Patients in subgroup of Cohort C (1-5 years old), given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received placebo orally once daily.

    Number of subjects in period 3 [2]
    Cohort A: High Dose OM in Periods 2 and 3 Cohort A: Low Dose OM in Periods 2 and 3 Cohort B: High Dose OM in Periods 2 and 3 Cohort B: Low Dose OM in Periods 2 and 3 Cohort C: OM in Periods 2, 3, and 4 Cohort A: Placebo in Period 3 (From High Dose in Period 2) Cohort A: Placebo in Period 3 (From Low Dose in Period 2) Cohort B: Placebo in Period 3 (From High Dose in Period 2) Cohort B: Placebo in Period 3 (From Low Dose in Period 2) Cohort C: Placebo in Period 3 (From OM in Period 2)
    Started
    48
    45
    26
    27
    29
    45
    44
    28
    26
    29
    Completed
    48
    45
    25
    26
    29
    42
    44
    27
    26
    28
    Not completed
    0
    0
    1
    1
    0
    3
    0
    1
    0
    1
         Protocol deviation
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
         Met blood pressure goal
    -
    -
    -
    1
    -
    -
    -
    -
    -
    -
         Unknown
    -
    -
    -
    -
    -
    1
    -
    1
    -
    -
         Adverse event, non-fatal
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
         Consent withdrawn by subject
    -
    -
    1
    -
    -
    -
    -
    -
    -
    -
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    Notes
    [2] - 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: This trial has a crossover component and multiple sub-groups, so the number of participants in each group is not as expected.
    Period 4
    Period 4 title
    Period 4:Open Label, Safety Analysis Set
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort A: Period 4 Open-label Olmesartan
    Arm description
    All remaining members of Cohort A (6-16 years old with a limit on the number of Black patients) were given 10 mg to 40 mg of olmesartan administered as oral suspension or tablets, depending on patient weight and response in the open-label Period 4 (weeks 6-51). Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received 10 mg olmesartan medoxomil suspension or 20 mg tablet(s) orally once daily for 46 weeks.

    Arm title
    Cohort B: Period 4 Open-label Olmesartan
    Arm description
    All remaining members of Cohort B (6-16 years old comprised exclusively of Black patients) were given 10 mg to 40 mg of olmesartan administered as oral suspension or tablets, depending on patient weight and response in the open-label Period 4 (weeks 6-51). Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received 10 mg olmesartan medoxomil suspension or 20 mg tablet(s) orally once daily for 46 weeks.

    Arm title
    Cohort C: OM in Periods 2, 3, and 4
    Arm description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C (who received OM in Periods 2 and 3) received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.
    Arm type
    Experimental

    Investigational medicinal product name
    Olmesartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Number of subjects in period 4
    Cohort A: Period 4 Open-label Olmesartan Cohort B: Period 4 Open-label Olmesartan Cohort C: OM in Periods 2, 3, and 4
    Started
    179
    104
    57
    Completed
    149
    83
    57
    Not completed
    30
    21
    0
         Protocol deviation
    1
    -
    -
         Non-compliance with Protocol
    4
    4
    -
         Physician decision
    -
    2
    -
         Unknown
    1
    3
    -
         Increased blood pressure
    1
    1
    -
         Adverse event, non-fatal
    1
    2
    -
         Consent withdrawn by subject
    5
    2
    -
         Lost to follow-up
    17
    7
    -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: High Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a high dose of olmesartan medoxomil suspension (OM), depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort A: Low Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort B: High Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort B: Low Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort C: OM in Periods 2, 3, and 4
    Reporting group description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Reporting group values
    Cohort A: High Dose OM in Periods 2 and 3 Cohort A: Low Dose OM in Periods 2 and 3 Cohort B: High Dose OM in Periods 2 and 3 Cohort B: Low Dose OM in Periods 2 and 3 Cohort C: OM in Periods 2, 3, and 4 Total
    Number of subjects
    95 95 56 56 60 362
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    12.1 ± 2.97 12.3 ± 2.98 12.2 ± 2.83 12.8 ± 2.42 3.4 ± 1.45 -
    Gender categorical
    Units: Subjects
        Female
    33 35 35 20 26 149
        Male
    62 60 21 36 34 213

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    All Patients
    Reporting group description
    Period 1 was a screening, wash-out period of approximately two weeks. All participants were included in the screening, wash-out period and during this period no intervention was administered.
    Reporting group title
    Cohort A: High Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a high dose of olmesartan medoxomil suspension (OM), depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort A: Low Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort B: High Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort B: Low Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort C: OM in Periods 2, 3, and 4
    Reporting group description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.
    Reporting group title
    Cohort A: High Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a high dose of olmesartan medoxomil suspension (OM), depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort A: Low Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort B: High Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort B: Low Dose OM in Periods 2 and 3
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black subjects) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period from day 0 to week 3). Half of the subjects continued this dose into Period 3 (double-blind, placebo controlled period from week 3 to week 5).

    Reporting group title
    Cohort C: OM in Periods 2, 3, and 4
    Reporting group description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Reporting group title
    Cohort A: Placebo in Period 3 (From High Dose in Period 2)
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black participants) given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous high dose of OM.

    Reporting group title
    Cohort A: Placebo in Period 3 (From Low Dose in Period 2)
    Reporting group description
    Patients in subgroup of Cohort A (6-16 years old with a limit on the number of Black patients) given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous low dose of OM.

    Reporting group title
    Cohort B: Placebo in Period 3 (From High Dose in Period 2)
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black patients), given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous high dose of OM.

    Reporting group title
    Cohort B: Placebo in Period 3 (From Low Dose in Period 2)
    Reporting group description
    Patients in subgroup of Cohort B (6-16 years old comprised exclusively of Black patients), given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5) instead of the previous low dose of OM.

    Reporting group title
    Cohort C: Placebo in Period 3 (From OM in Period 2)
    Reporting group description
    Patients in subgroup of Cohort C (1-5 years old), given placebo during Period 3 (double-blind, placebo-controlled period from week 3 to week 5).
    Reporting group title
    Cohort A: Period 4 Open-label Olmesartan
    Reporting group description
    All remaining members of Cohort A (6-16 years old with a limit on the number of Black patients) were given 10 mg to 40 mg of olmesartan administered as oral suspension or tablets, depending on patient weight and response in the open-label Period 4 (weeks 6-51). Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Reporting group title
    Cohort B: Period 4 Open-label Olmesartan
    Reporting group description
    All remaining members of Cohort B (6-16 years old comprised exclusively of Black patients) were given 10 mg to 40 mg of olmesartan administered as oral suspension or tablets, depending on patient weight and response in the open-label Period 4 (weeks 6-51). Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Reporting group title
    Cohort C: OM in Periods 2, 3, and 4
    Reporting group description
    Patients in subgroup of cohort C (1-5 years old) were given olmesartan medoxomil 0.3 mg/kg in Period 2 (open-label period from day 0 to week 3) and patients in a subgroup of Cohort C were given that dose of OM during Period 3 (double-blind, placebo controlled period from week 3 to week 5). In Period 4 (open-label period from weeks 6-51), all patients in Cohort C (who received OM in Periods 2 and 3) received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks, the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Subject analysis set title
    Cohort A: High Dose OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subgroup of Cohort A (6-16 years old with a limit on the number of Black participants) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period).

    Subject analysis set title
    Cohort A: Low Dose OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subgroup of Cohort A (6-16 years old with a limit on the number of Black participants) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period).

    Subject analysis set title
    Cohort B: High Dose OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subgroup of Cohort B (6-16 years old comprised exclusively of Black participants) given a high dose (20 mg or 40 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period).

    Subject analysis set title
    Cohort B: Low Dose OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subgroup of Cohort B (6-16 years old comprised exclusively of Black participants) given a low dose (2.5 mg or 5.0 mg) of olmesartan medoxomil suspension (OM) depending on weight during Period 2 (double-blind, dose-response period). Half of the participants continued this dose into Period 3 (double-blind, placebo controlled period).

    Subject analysis set title
    Cohort C: OM (Olmesartan Medoxomil)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort C (1-5 years old) was given olmesartan medoxomil (OM) 0.3 mg/kg in Period 2 (open-label period) and a subgroup of Cohort C was given that dose of OM during Period 3 (double-blind, placebo-controlled period). In Period 4 (open-label period), all of Cohort C received an OM starting dose of 0.3 mg/kg. If hypertension was not controlled after two week the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Subject analysis set title
    Cohort A
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort A participants were 6-16 years old with a limit on the number of Black participants. Includes participants randomized to both the high dose of olmesartan medoxomil suspension (20 mg or 40 mg) and the low dose (2.5 mg or 5.0mg), depending on weight, administered once daily.

    Subject analysis set title
    Cohort B
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort B participants were 6-16 years old and comprised exclusively of Black participants. Includes participants randomized to both the high dose of olmesartan medoxomil suspension (20 mg or 40 mg) and the low dose (2.5 mg or 5.0 mg), depending on weight, administered once daily.

    Subject analysis set title
    Cohorts A + B
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort A + B participants were 6-16 years old. Cohort A limited the number of Black participants, while Cohort B was comprised exclusively of Black participants. Includes participants randomized to both the high dose of olmesartan medoxomil suspension (20 mg or 40 mg) and the low dose (2.5 mg or 5.0mg), depending on weight, administered once daily.

    Subject analysis set title
    Cohorts A + B: Low Dose OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subgroup from Cohorts A + B (6-16 years old) who received the low dose of olmesartan medoxomil suspension (OM 2.5 mg or 5.0 mg depending on weight), administered once daily in Period 2. Cohort A limited the number of Black participants, while Cohort B was comprised exclusively of Black participants.

    Subject analysis set title
    Cohorts A + B: High Dose OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subgroup from Cohorts A + B (6-16 years old) who received the high dose of olmesartan medoxomil suspension (OM 20 mg or 40 mg depending on weight), administered once daily in Period 2. Cohort A limited the number of Black participants, while Cohort B was comprised exclusively of Black participants.

    Subject analysis set title
    Cohort A: OM Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort A participants were 6-16 years old with a limit on the number of Black participants. Includes participants randomized to both the high dose of olmesartan medoxomil suspension (OM 20 mg or 40 mg) and the low dose (2.5 mg or 5.0mg), depending on weight, administered once daily in period 2, and continued that dosage into period 3.

    Subject analysis set title
    Cohort A: Placebo Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort A participants were 6-16 years old with a limit on the number of Black participants. Includes participants randomized to both the high and low dose of olmesartan medoxomil suspension in period 2, and changed to placebo in period 3.

    Subject analysis set title
    Cohort B: OM Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort B participants were 6-16 years old and comprised exclusively of Black participants. Includes participants randomized to both the high dose of olmesartan medoxomil suspension (OM 20 mg or 40 mg) and the low dose (2.5 mg or 5.0mg), depending on weight, administered once daily in period 2, and continued that dosage into period 3.

    Subject analysis set title
    Cohort B: Placebo Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort B participants were 6-16 years old and comprised exclusively of Black participants. Includes participants randomized to both the high and low dose of olmesartan medoxomil suspension in period 2, and changed to placebo in period 3.

    Subject analysis set title
    Cohorts A + B: OM Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort A + B participants were 6-16 years old. Includes participants randomized to both the high dose of olmesartan medoxomil suspension (OM 20 mg or 40 mg) and the low dose (2.5 mg or 5.0mg), depending on weight, administered once daily in period 2, and continued that dosage into period 3.

    Subject analysis set title
    Cohorts A + B: Placebo Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohorts A + B participants were 6-16 years old. Includes participants randomized to both the high and low dose of olmesartan medoxomil suspension in period 2, and changed to placebo in period 3.

    Subject analysis set title
    Cohort C: OM Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort C consisted of children from 1 to 5 years of age. There were no racial restrictions. This group continued on its Period 2 olmesartan dose of 0.3 mg/kg.

    Subject analysis set title
    Cohort C: Placebo Period 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort C consisted of children from 1 to 5 years of age. There were no racial restrictions. This group was switched from its Period 2 olmesartan dose of 0.3 mg/kg to placebo.

    Subject analysis set title
    Cohorts A + B: Period 4 Open-label OM
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects of Cohorts A + B (6-16 years old) were given 10 mg to 40 mg of olmesartan (OM) administered as oral suspension or tablets depending on participant weight and response in the openlabel Period 4. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Primary: Least Squares Mean Change from Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 weeks)

    Close Top of page
    End point title
    Least Squares Mean Change from Baseline in Seated Systolic Blood Pressure to the End of Period 2 (3 weeks)
    End point description
    The efficacy dose response change in trough seated systolic blood pressure (both non-weight adjusted and weight adjusted results) from baseline to the end of the dose-ranging period (Period 2). Non-weight adjusted dose was the fixed olmesartan medoxomil dose; weight adjusted dose calculated mg of olmesartan medoxomil per kg of weight at baseline. The number of participants includes all randomized to Cohort A, Cohort B and a combination of the two cohorts. The Last Observation Carried Forward method was used in the linear regression analysis for the change in the seated systolic blood pressure from baseline to the end of three weeks.
    End point type
    Primary
    End point timeframe
    Day 0 to 3 weeks
    End point values
    Cohort A Cohort B Cohorts A + B
    Number of subjects analysed
    190
    112
    302
    Units: millimeter of mercury (mm Hg)
    least squares mean (standard error)
        Non-weight adjusted dosage
    -0.69 ± 0.202
    -0.85 ± 0.282
    -0.75 ± 0.165
        Weight adjusted dosage
    -8.97 ± 2.054
    -7.17 ± 3.19
    -8.36 ± 1.75
    Statistical analysis title
    Cohort A Non-weight adjusted dosage
    Comparison groups
    Cohort A v Cohort B v Cohorts A + B
    Number of subjects included in analysis
    604
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0008
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Cohort A Weight adjusted dosage
    Comparison groups
    Cohort A v Cohort B v Cohorts A + B
    Number of subjects included in analysis
    604
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Cohort B Non-weight adjusted dosage
    Comparison groups
    Cohort B v Cohort A v Cohorts A + B
    Number of subjects included in analysis
    604
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0032
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Cohort B Weight adjusted dosage
    Comparison groups
    Cohort B v Cohort A v Cohorts A + B
    Number of subjects included in analysis
    604
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Cohorts A + B Weight adjusted dosage
    Comparison groups
    Cohorts A + B v Cohort A v Cohort B
    Number of subjects included in analysis
    604
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Cohorts A + B Non-weight adjusted dosage
    Comparison groups
    Cohorts A + B v Cohort A v Cohort B
    Number of subjects included in analysis
    604
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval

    Primary: Mean Change from Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 weeks)

    Close Top of page
    End point title
    Mean Change from Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 2 (3 weeks)
    End point description
    Mean change from baseline to the end of the dose ranging period in systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined. The Intent-to-Treat (ITT) population for Period II of the study was defined as subjects who took at least one dose of study medication and had study baseline and at least one seated systolic, or diastolic blood pressure measurement after taking study medication. The Last Observation carried forward was used.
    End point type
    Primary
    End point timeframe
    Day 0 (baseline) to 3 weeks
    End point values
    Cohort A: High Dose OM Cohort A: Low Dose OM Cohort B: High Dose OM Cohort B: Low Dose OM Cohorts A + B: Low Dose OM Cohorts A + B: High Dose OM
    Number of subjects analysed
    94
    94
    56
    56
    150
    150
    Units: mm Hg
    arithmetic mean (standard deviation)
        Change in Systolic Blood Pressure
    -12.58 ± 10.157
    -7.76 ± 9.18
    -10.68 ± 9.259
    -4.73 ± 11.483
    -6.63 ± 10.17
    -11.87 ± 9.843
        Change in Diastolic Blood Pressure
    -9.5 ± 9.757
    -5.52 ± 8.058
    -7.58 ± 8.172
    -3.49 ± 8.844
    -4.76 ± 8.389
    -8.78 ± 9.216
    Statistical analysis title
    Statistical Analysis_1
    Statistical analysis description
    A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort A: High Dose OM v Cohort A: Low Dose OM
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.0008
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_2
    Statistical analysis description
    A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort A: Low Dose OM v Cohort A: High Dose OM
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.0026
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_3
    Statistical analysis description
    A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort B: Low Dose OM v Cohort B: High Dose OM
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.0032
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_5
    Statistical analysis description
    A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohorts A + B: Low Dose OM v Cohorts A + B: High Dose OM
    Number of subjects included in analysis
    300
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_4
    Statistical analysis description
    A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort B: Low Dose OM v Cohort B: High Dose OM
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.0125
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_6
    Statistical analysis description
    A linear regression analysis of olmesartan dose (non-weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohorts A + B: Low Dose OM v Cohorts A + B: High Dose OM
    Number of subjects included in analysis
    300
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_7
    Statistical analysis description
    A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort A: Low Dose OM v Cohort A: High Dose OM
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_8
    Statistical analysis description
    A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort A: Low Dose OM v Cohort A: High Dose OM
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_9
    Statistical analysis description
    A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort B: Low Dose OM v Cohort B: High Dose OM
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.0265
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_10
    Statistical analysis description
    A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohort B: Low Dose OM v Cohort B: High Dose OM
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.0084
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_11
    Statistical analysis description
    A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated systolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohorts A + B: Low Dose OM v Cohorts A + B: High Dose OM
    Number of subjects included in analysis
    300
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001
    Method
    Regression, Linear
    Confidence interval
    Statistical analysis title
    Statistical Analysis_12
    Statistical analysis description
    A linear regression analysis of olmesartan dose (weight adjusted) on the change from baseline in seated diastolic blood pressure was carried out. The null hypothesis of zero-slope was tested.
    Comparison groups
    Cohorts A + B: Low Dose OM v Cohorts A + B: High Dose OM
    Number of subjects included in analysis
    300
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001
    Method
    Regression, Linear
    Parameter type
    Slope
    Confidence interval

    Secondary: Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3

    Close Top of page
    End point title
    Mean Change From Period 3 Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 3
    End point description
    Mean change from period 3 baseline (completion of the dose adjustment period and prior to starting the treatment of period 3) to the end of period 3 (double-blind placebo-controlled period) in seated systolic and diastolic blood pressure readings for Cohort A, Cohort B, Cohorts A+B combined and Cohort C. Intent to treat population defined as subjects who finished Period 2, had the end of Period 2 seated systolic or diastolic blood pressure measurement, took the Period 3 study medication for at least one week, and had the end of Period 3 seated systolic or diastolic blood pressure measurement. Intent-to-treat population defined as subjects who finished Period 2, had the end of Period 2 seated systolic or diastolic blood pressure measurement, took the Period 3 study medication for at least one week, and had the end of Period 3 seated systolic or diastolic blood pressure measurement.
    End point type
    Secondary
    End point timeframe
    Week 3 (period 3 baseline) to week 5 (end of Period 3)
    End point values
    Cohort A: OM Period 3 Cohort A: Placebo Period 3 Cohort B: OM Period 3 Cohort B: Placebo Period 3 Cohorts A + B: OM Period 3 Cohorts A + B: Placebo Period 3 Cohort C: OM Period 3 Cohort C: Placebo Period 3
    Number of subjects analysed
    93
    89
    53
    54
    146
    143
    29
    29
    Units: mm Hg
    arithmetic mean (standard deviation)
        Change in Systolic Blood Pressure
    0.43 ± 9.46
    4.93 ± 9.62
    1.37 ± 9.5
    3.79 ± 10
    0.77 ± 9.451
    4.5 ± 9.745
    1.36 ± 8.994
    4.95 ± 8.568
        Change in Diastolic Blood Pressure
    0.24 ± 8.12
    4.43 ± 10.15
    1.94 ± 7.1
    3.25 ± 8.74
    0.85 ± 7.79
    3.99 ± 9.627
    0.31 ± 8.556
    3.77 ± 7.203
    Statistical analysis title
    Statistical Analysis_1
    Statistical analysis description
    Analysis of systolic blood pressure. Null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 93 for Cohort A: OM Period 3 and 89 for Cohort A: Placebo Period 3.
    Comparison groups
    Cohort A: OM Period 3 v Cohort A: Placebo Period 3
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0093
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -3.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.27
         upper limit
    -0.89
    Statistical analysis title
    Statistical Analysis_2
    Statistical analysis description
    Analysis for diastolic blood pressure. The null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 93 for Cohort A: OM Period 3 and 89 for Cohort A: Placebo Period 3.
    Comparison groups
    Cohort A: OM Period 3 v Cohort A: Placebo Period 3
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0052
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -3.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.92
         upper limit
    -1.05
    Statistical analysis title
    Statistical Analysis_3
    Statistical analysis description
    Analysis of systolic blood pressure. Null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 53 for Cohort B: OM Period 3 and 54 for Cohort B: Placebo Period 3.
    Comparison groups
    Cohort B: OM Period 3 v Cohort B: Placebo Period 3
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.133
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -2.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.93
         upper limit
    0.79
    Statistical analysis title
    Statistical Analysis_4
    Statistical analysis description
    Analysis for diastolic blood pressure. The null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 53 for Cohort B: OM Period 3 and 54 for Cohort B: Placebo Period 3.
    Comparison groups
    Cohort B: OM Period 3 v Cohort B: Placebo Period 3
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3442
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -1.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.27
         upper limit
    1.5
    Statistical analysis title
    Statistical Analysis_5
    Statistical analysis description
    For seated systolic blood pressure the null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 146 for Cohorts A + B: OM Period 3 and 143 for Cohorts A + B: Placebo Period 3.
    Comparison groups
    Cohorts A + B: OM Period 3 v Cohorts A + B: Placebo Period 3
    Number of subjects included in analysis
    289
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0029
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -3.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.24
         upper limit
    -1.09
    Statistical analysis title
    Statistical Analysis_6
    Statistical analysis description
    For seated diastolic blood pressure the null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 146 for Cohorts A + B: OM Period 3 and 143 for Cohorts A + B: Placebo Period 3.
    Comparison groups
    Cohorts A + B: OM Period 3 v Cohorts A + B: Placebo Period 3
    Number of subjects included in analysis
    289
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0032
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -2.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.65
         upper limit
    -0.95
    Statistical analysis title
    Statistical Analysis_7
    Statistical analysis description
    For seated systolic blood pressure the null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 29 for Cohort C: OM Period 3 and 29 for Cohort C: Placebo Period 3.
    Comparison groups
    Cohort C: OM Period 3 v Cohort C: Placebo Period 3
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2113
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -2.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.29
         upper limit
    1.65
    Statistical analysis title
    Statistical Analysis_8
    Statistical analysis description
    For seated diastolic blood pressure the null hypothesis of no treatment difference was tested. The number of subjects included in analysis was 29 for Cohort C: OM Period 3 and 29 for Cohort C: Placebo Period 3.
    Comparison groups
    Cohort C: OM Period 3 v Cohort C: Placebo Period 3
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1496
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -2.92
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.92
         upper limit
    1.09

    Secondary: Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (end of study)

    Close Top of page
    End point title
    Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (end of study)
    End point description
    Mean change from baseline to the end of the open label Period 4 in seated systolic and diastolic blood pressure readings for Cohort A, Cohort B and Cohorts A+B combined. Intent to treat population includes participants with at least one visit in Period 4.
    End point type
    Secondary
    End point timeframe
    Day 0 to week 51 (end of study)
    End point values
    Cohorts A + B: Period 4 Open-label OM
    Number of subjects analysed
    281
    Units: mm Hg
    arithmetic mean (standard deviation)
        Change in Systolic Blood Pressure
    -9.7 ± 11.01
        Change in Diastolic Blood Pressure
    -6.6 ± 9.41
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) for Cohort C

    Close Top of page
    End point title
    Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure Measurements to the End of Period 4 (End of Study) for Cohort C
    End point description
    Mean change from baseline to the end of the open label Period 4 in seated systolic and diastolic blood pressure readings for Cohort C. Subjects included who received medication in Period 4.
    End point type
    Secondary
    End point timeframe
    Day 0 to week 51 week (end of study)
    End point values
    Cohort C: OM (Olmesartan Medoxomil)
    Number of subjects analysed
    57
    Units: mm Hg
    arithmetic mean (standard deviation)
        Change in Systolic Blood Pressure
    -15.7 ± 9.83
        Change in Diastolic Blood Pressure
    -13.3 ± 11.18
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected starting with the signing of the informed consent form and continuing through the end of the study (51 weeks).
    Adverse event reporting additional description
    AEs observed by the investigator, or reported by the subject, and any remedial action taken, were recorded in the case report form by the investigator. The nature of each event, time of onset after drug administration, duration, and intensity were documented together with the investigator’s opinion of the causal relationship to the treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    8.1
    Reporting groups
    Reporting group title
    Cohort A: Period 2 Low Dose OM
    Reporting group description
    For Cohort A (patients 6-16 years old) olmesartan medoxomil suspension (OM) providing 2.5 mg or 5 mg, depending on weight

    Reporting group title
    Cohort A: Period 2 High Dose OM
    Reporting group description
    For Cohort A (patients 6-16 years old), olmesartan medoxomil suspension (OM) providing 20 mg or 40 mg, depending on weight

    Reporting group title
    Cohort A: Period 3 OM High Dose Continued
    Reporting group description
    The 20 mg or 40 mg dose of olmesartan medoxomil suspension (OM) from the previous period was continued.

    Reporting group title
    Cohort A: Period 3 Placebo From High Dose
    Reporting group description
    Placebo was given instead of the previous high dose of olmesartan.

    Reporting group title
    Cohort A: Period 3 OM Low Dose Continued
    Reporting group description
    The 2.5 mg or 5 mg dose of olmesartan medoxomil suspension (OM) from the previous period was continued.

    Reporting group title
    Cohort A: Period 3 Placebo From Low Dose
    Reporting group description
    Placebo was given instead of the previous low dose of olmesartan.

    Reporting group title
    Cohort A: Period 4 Open-label OM
    Reporting group description
    10 mg to 40 mg of olmesartan was administered as oral suspension or tablets depending on patient weight and response. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Reporting group title
    Cohort B: Period 2 High Dose OM
    Reporting group description
    For Cohort B (participants 6-16 years old), olmesartan medoxomil suspension (OM) providing 20 mg or 40 mg, depending on weight.

    Reporting group title
    Cohort B: Period 2 Low Dose OM
    Reporting group description
    For Cohort B (participants 6-16 years old), olmesartan medoxomil suspension (OM) providing 2.5 mg or 5 mg, depending on weight.

    Reporting group title
    Cohort B: Period 3 Placebo From High Dose
    Reporting group description
    Placebo was given instead of the previous high dose of olmesartan.

    Reporting group title
    Cohort B: Period 3 OM Low Dose Continued
    Reporting group description
    The 2.5 mg or 5 mg dose of olmesartan medoxomil suspension (OM) from the previous period was continued.

    Reporting group title
    Cohort B: Period 3 OM High Dose Continued
    Reporting group description
    The 20 mg or 40 mg dose of olmesartan medoximil suspension (OM) from the previous period was continued.

    Reporting group title
    Cohort C: Period 3 Placebo From OM in Period 2
    Reporting group description
    The 0.3 mg/kg dose of olmesartan medoxomil suspension (OM) was discontinued for these participants. They were switched to placebo.

    Reporting group title
    Cohort B: Period 3 Placebo From Low Dose
    Reporting group description
    Placebo was given instead of the previous low dose of olmesartan.

    Reporting group title
    Cohort B: Period 4 Open-label OM
    Reporting group description
    10 mg to 40 mg of olmesartan was administered as oral suspension or tablets depending on patient weight and response. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Reporting group title
    Cohort C: Period 2 Open-label OM
    Reporting group description
    The dose of olmesarten medoxomil suspension (OM) was 0.3 mg/kg for all patients who were 1 to 5 years of age.

    Reporting group title
    Cohort C: Period 3 OM Dose Continued
    Reporting group description
    The 0.3 mg/kg dose of OM was continued for these patients.

    Reporting group title
    Cohort C: Period 4 Open-label OM
    Reporting group description
    Patients received an olmesartan medoxomil suspension (OM) starting dose of 0.3 mg/kg. If hypertension was not controlled after two weeks the dose was doubled. Additional antihypertensive drugs (not an angiotensin converting enzyme or angiotensin receptor blocker) were allowed if hypertension was not controlled.

    Serious adverse events
    Cohort A: Period 2 Low Dose OM Cohort A: Period 2 High Dose OM Cohort A: Period 3 OM High Dose Continued Cohort A: Period 3 Placebo From High Dose Cohort A: Period 3 OM Low Dose Continued Cohort A: Period 3 Placebo From Low Dose Cohort A: Period 4 Open-label OM Cohort B: Period 2 High Dose OM Cohort B: Period 2 Low Dose OM Cohort B: Period 3 Placebo From High Dose Cohort B: Period 3 OM Low Dose Continued Cohort B: Period 3 OM High Dose Continued Cohort C: Period 3 Placebo From OM in Period 2 Cohort B: Period 3 Placebo From Low Dose Cohort B: Period 4 Open-label OM Cohort C: Period 2 Open-label OM Cohort C: Period 3 OM Dose Continued Cohort C: Period 4 Open-label OM
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 95 (1.05%)
    2 / 95 (2.11%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    20 / 179 (11.17%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    7 / 104 (6.73%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    6 / 57 (10.53%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Laparoscopy
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Coarctation of the aorta
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    1 / 104 (0.96%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    1 / 104 (0.96%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Eye hemorrhage
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ophthalmoplegia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Anasarca
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Peritonitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    1 / 104 (0.96%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    2 / 179 (1.12%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 95 (1.05%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureteric stenosis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    1 / 104 (0.96%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    2 / 179 (1.12%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    1 / 104 (0.96%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoproteinemia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic disorder
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abcess limb
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    1 / 104 (0.96%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    1 / 179 (0.56%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Broncopneumonia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    3 / 179 (1.68%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    2 / 57 (3.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    2 / 179 (1.12%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory infection
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 95 (1.05%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    Cohort A: Period 2 Low Dose OM Cohort A: Period 2 High Dose OM Cohort A: Period 3 OM High Dose Continued Cohort A: Period 3 Placebo From High Dose Cohort A: Period 3 OM Low Dose Continued Cohort A: Period 3 Placebo From Low Dose Cohort A: Period 4 Open-label OM Cohort B: Period 2 High Dose OM Cohort B: Period 2 Low Dose OM Cohort B: Period 3 Placebo From High Dose Cohort B: Period 3 OM Low Dose Continued Cohort B: Period 3 OM High Dose Continued Cohort C: Period 3 Placebo From OM in Period 2 Cohort B: Period 3 Placebo From Low Dose Cohort B: Period 4 Open-label OM Cohort C: Period 2 Open-label OM Cohort C: Period 3 OM Dose Continued Cohort C: Period 4 Open-label OM
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    46 / 95 (48.42%)
    47 / 95 (49.47%)
    15 / 48 (31.25%)
    6 / 45 (13.33%)
    9 / 45 (20.00%)
    6 / 44 (13.64%)
    128 / 179 (71.51%)
    9 / 56 (16.07%)
    12 / 56 (21.43%)
    1 / 28 (3.57%)
    2 / 27 (7.41%)
    4 / 26 (15.38%)
    8 / 29 (27.59%)
    1 / 26 (3.85%)
    56 / 104 (53.85%)
    12 / 59 (20.34%)
    4 / 29 (13.79%)
    46 / 57 (80.70%)
    Investigations
    Blood urea increased
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Pharyngolaryngeal pain
         subjects affected / exposed
    6 / 95 (6.32%)
    1 / 95 (1.05%)
    2 / 48 (4.17%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 44 (2.27%)
    12 / 179 (6.70%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    1 / 28 (3.57%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    3 / 104 (2.88%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    7
    1
    2
    0
    1
    1
    20
    0
    0
    1
    0
    0
    0
    0
    3
    0
    0
    0
    Cough
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    3 / 48 (6.25%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 44 (2.27%)
    24 / 179 (13.41%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    1 / 29 (3.45%)
    0 / 26 (0.00%)
    7 / 104 (6.73%)
    3 / 59 (5.08%)
    1 / 29 (3.45%)
    5 / 57 (8.77%)
         occurrences all number
    0
    0
    3
    0
    1
    1
    28
    0
    0
    0
    0
    1
    1
    0
    8
    3
    1
    6
    Rhinorrhea
         subjects affected / exposed
    3 / 95 (3.16%)
    2 / 95 (2.11%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 44 (0.00%)
    4 / 179 (2.23%)
    0 / 56 (0.00%)
    1 / 56 (1.79%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    3
    2
    0
    0
    2
    0
    4
    0
    1
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    3 / 179 (1.68%)
    0 / 56 (0.00%)
    1 / 56 (1.79%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    5 / 104 (4.81%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    2 / 57 (3.51%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    9
    0
    1
    0
    0
    0
    0
    0
    5
    0
    0
    3
    Nasal congestion
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    9 / 179 (5.03%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    10
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Asthma
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    6 / 179 (3.35%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    6 / 57 (10.53%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    11
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    8
    Rhinitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    2 / 29 (6.90%)
    4 / 57 (7.02%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 95 (2.11%)
    9 / 95 (9.47%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    10 / 179 (5.59%)
    1 / 56 (1.79%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 29 (3.45%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    2
    11
    0
    0
    0
    0
    13
    1
    0
    0
    0
    0
    1
    0
    4
    0
    0
    0
    Headache
         subjects affected / exposed
    7 / 95 (7.37%)
    14 / 95 (14.74%)
    4 / 48 (8.33%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    2 / 44 (4.55%)
    30 / 179 (16.76%)
    5 / 56 (8.93%)
    3 / 56 (5.36%)
    0 / 28 (0.00%)
    1 / 27 (3.70%)
    2 / 26 (7.69%)
    0 / 29 (0.00%)
    1 / 26 (3.85%)
    18 / 104 (17.31%)
    1 / 59 (1.69%)
    0 / 29 (0.00%)
    1 / 57 (1.75%)
         occurrences all number
    11
    24
    5
    1
    3
    2
    42
    5
    3
    0
    1
    2
    0
    1
    38
    1
    0
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 95 (4.21%)
    4 / 95 (4.21%)
    3 / 48 (6.25%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    16 / 179 (8.94%)
    1 / 56 (1.79%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    3 / 59 (5.08%)
    0 / 29 (0.00%)
    7 / 57 (12.28%)
         occurrences all number
    4
    4
    3
    0
    0
    0
    21
    1
    0
    0
    0
    0
    0
    0
    2
    3
    0
    8
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    5 / 95 (5.26%)
    3 / 95 (3.16%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    10 / 179 (5.59%)
    1 / 56 (1.79%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    9 / 104 (8.65%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    7
    3
    0
    0
    0
    0
    10
    1
    0
    0
    0
    0
    0
    0
    15
    0
    0
    0
    Vomiting
         subjects affected / exposed
    3 / 95 (3.16%)
    1 / 95 (1.05%)
    3 / 48 (6.25%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    11 / 179 (6.15%)
    0 / 56 (0.00%)
    1 / 56 (1.79%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    7 / 104 (6.73%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    3 / 57 (5.26%)
         occurrences all number
    3
    1
    3
    0
    0
    0
    17
    0
    1
    0
    0
    0
    0
    0
    7
    0
    0
    3
    Diarrhea
         subjects affected / exposed
    2 / 95 (2.11%)
    1 / 95 (1.05%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    2 / 179 (1.12%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 29 (3.45%)
    0 / 26 (0.00%)
    3 / 104 (2.88%)
    1 / 59 (1.69%)
    0 / 29 (0.00%)
    4 / 57 (7.02%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    1
    0
    3
    1
    0
    5
    Renal and urinary disorders
    Nephrotic syndrome
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    2 / 104 (1.92%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    5 / 57 (8.77%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    7
    Proteinurea
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    3 / 57 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    Metabolism and nutrition disorders
    Pseudohyperkalemia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    2 / 29 (6.90%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 95 (4.21%)
    1 / 95 (1.05%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    16 / 179 (8.94%)
    1 / 56 (1.79%)
    2 / 56 (3.57%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    2 / 29 (6.90%)
    0 / 26 (0.00%)
    4 / 104 (3.85%)
    1 / 59 (1.69%)
    0 / 29 (0.00%)
    2 / 57 (3.51%)
         occurrences all number
    4
    1
    0
    0
    0
    0
    17
    1
    2
    0
    0
    0
    2
    0
    6
    1
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 95 (4.21%)
    7 / 95 (7.37%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    20 / 179 (11.17%)
    0 / 56 (0.00%)
    2 / 56 (3.57%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    3 / 104 (2.88%)
    1 / 59 (1.69%)
    1 / 29 (3.45%)
    11 / 57 (19.30%)
         occurrences all number
    4
    7
    0
    0
    0
    0
    25
    0
    2
    0
    0
    0
    0
    0
    6
    1
    1
    15
    Influenza
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 95 (1.05%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 44 (4.55%)
    10 / 179 (5.59%)
    0 / 56 (0.00%)
    2 / 56 (3.57%)
    0 / 28 (0.00%)
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    1 / 29 (3.45%)
    0 / 26 (0.00%)
    4 / 104 (3.85%)
    1 / 59 (1.69%)
    1 / 29 (3.45%)
    3 / 57 (5.26%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    12
    0
    2
    0
    1
    1
    1
    0
    4
    1
    1
    3
    Pharyngitis
         subjects affected / exposed
    2 / 95 (2.11%)
    4 / 95 (4.21%)
    0 / 48 (0.00%)
    3 / 45 (6.67%)
    2 / 45 (4.44%)
    0 / 44 (0.00%)
    7 / 179 (3.91%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    2 / 57 (3.51%)
         occurrences all number
    2
    4
    0
    3
    2
    0
    7
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Otitis media acute
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    1 / 59 (1.69%)
    0 / 29 (0.00%)
    3 / 57 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    4
    Tonsilitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    5 / 57 (8.77%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    8
    Urinary tract infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    4 / 179 (2.23%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    4 / 57 (7.02%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    4
    Viral infection
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 95 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 44 (0.00%)
    0 / 179 (0.00%)
    0 / 56 (0.00%)
    0 / 56 (0.00%)
    0 / 28 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 29 (0.00%)
    0 / 26 (0.00%)
    0 / 104 (0.00%)
    0 / 59 (0.00%)
    0 / 29 (0.00%)
    3 / 57 (5.26%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 May 2005
    The amendment was included to increase the number of subjects in Cohort C from 50 to 60, added glomerular kidney disease to the definition of subjects with hypertension as greater than or equal to (>=)90th percentile in the inclusion criteria, added greater than (>) 2 standard deviation (SD) to the exclusion criteria for seated systolic blood pressure (SeSBP) / seated diastolic blood pressure (SeDBP) in subjects with malignant hypertension, changed the primary efficacy analysis to include the change from baseline in SeDBP, and amended statistical analyses to include examination of Cohorts A, B, and A + B combined.
    06 Mar 2006
    The amendment was included to clarified conditions for interpretation of screening potassium levels, added angiotensin converting enzyme (ACE) inhibitors as an excluded antihypertensive medication during Period IV, added SeDBP to the definition of malignant hypertension, and identified the central clinical laboratory.

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA