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    Clinical Trial Results:
    A Randomized, Double-Blind, Efficacy and Safety Study of AR 14 (AZILSARTAN MEDOXOMIL) Treatment and Withdrawal, Followed by an Open-Label Extension, in Children 6 to Less Than 18 Years of Age With Hypertension

    Summary
    EudraCT number
    		 2014-000674-18
    Trial protocol
    		 HU   IT   BG  
    Global end of trial date
    11 Nov 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 May 2022
    First version publication date
    29 May 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AR14.001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02235909
    WHO universal trial number (UTN)
    		 U1111-1162-3595
    Sponsors
    Sponsor organisation name
    Arbor Pharmaceuticals, LLC
    Sponsor organisation address
    6 Concourse Parkway Suite 1800, Atlanta, United States, GA 30328
    Public contact
    Steven Caras, M.D., Ph.D, Arbor Pharmaceuticals, LLC, Steven.Caras@arborpharma.com
    Scientific contact
    Steven Caras, M.D., Ph.D, Arbor Pharmaceuticals, LLC, Steven.Caras@arborpharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000237-PIP01-08
    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
    11 Nov 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Nov 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of the study is to evaluate the antihypertensive effect of azilsartan medoxomil (AZM) compared with placebo after a randomized, double-blind, withdrawal (Withdrawal Phase).
    Protection of trial subjects
    All parents/legal guardians were required to read and sign an Informed Consent Form for participants.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Mar 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    South Africa: 35
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Ukraine: 15
    Country: Number of subjects enrolled
    United States: 38
    Country: Number of subjects enrolled
    Argentina: 2
    Country: Number of subjects enrolled
    Brazil: 12
    Country: Number of subjects enrolled
    Bulgaria: 13
    Country: Number of subjects enrolled
    Colombia: 6
    Country: Number of subjects enrolled
    Hungary: 44
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Mexico: 13
    Country: Number of subjects enrolled
    Poland: 26
    Worldwide total number of subjects
    215
    EEA total number of subjects
    87
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    49
    Adolescents (12-17 years)
    166
    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
    		 Participants took part in the study at 67 investigative sites in Argentina, Brazil, Bulgaria, Colombia, Hungary, Italy, Mexico, Poland, South Africa, Turkey, Ukraine, and the United States from 30 March 2015 to 11 November 2019.

    Pre-assignment
    Screening details
    		 Participants with hypertension first initially participated in the Run-in Phase/Washout Phase (Days -28 to 1), following that 215 participants were enrolled in Double-blind (DB) Phase, following DB Phase, 203 participants were enrolled in Withdrawal (WD) Phase and following WD Phase, 197 participants were enrolled in the Open-label (OL) Phase.

    Period 1
    Period 1 title
    Double-Blind Phase (Up to Week 6)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DB Phase: Losartan 25 mg + 50 mg + 100 mg
    Arm description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the losartan in the DB Phase. Participants with body weight >=25 to <50 kg were randomized to receive losartan 25 mg orally once daily, from Weeks 0 to 2 and losartan 50 mg from Weeks 2 to 6 and participants with body weight >=50 kg received losartan orally once daily 50 mg, from Weeks 0 to 2 and losartan 100 mg from Weeks 2 to 6 in the DB Phase.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Losartan potassium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Losartan over encapsulated tablets, 25 mg, orally

    Investigational medicinal product name
    Losartan potassium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Losartan over encapsulated tablets, 50 mg, orally

    Investigational medicinal product name
    Losartan potassium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Losartan over encapsulated tablets, 100 mg, orally

    Arm title
    		 DB Phase: Low-Dose Azilsartan Medoxomil (AZM-L) 10 mg
    Arm description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the low-dose AZM-L DB Phase. Participants with body weight >= 25 to <50 kg or >= 50 kg received AZM-L 10 mg, orally, once daily from Week 0-6 in the DB Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 10 mg, orally

    Arm title
    		 DB Phase: AZM-M 10 mg+20 mg
    Arm description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive Intermediate-Dose Azilsartan Medoxomil (AZM-M) in the DB Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-M orally, once daily 10 mg from Weeks 0-2 and AZM-M 20 mg from Weeks 2-6 in the DB Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 10 mg, orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 20 mg, orally

    Arm title
    		 DB Phase: AZM-H 10 mg + 40 mg/ 80 mg
    Arm description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive High-Dose Azilsartan Medoxomil (AZM-H) in the DB Phase. Participants with body weight >=25 to <50 kg received AZM-H orally, once daily 10 mg from Weeks 0-2 and AZM-H 40 mg from Weeks 2-6 and participants with body weight >=50 kg received AZM-H orally, once daily 10 mg from Weeks 0-2 and AZM-H 80 mg from Weeks 2-6 in the DB Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 10 mg, orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 80 mg, orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 40 mg, orally

    Number of subjects in period 1
    		DB Phase: Losartan 25 mg + 50 mg + 100 mg DB Phase: Low-Dose Azilsartan Medoxomil (AZM-L) 10 mg DB Phase: AZM-M 10 mg+20 mg DB Phase: AZM-H 10 mg + 40 mg/ 80 mg
    Started
    53
    52
    56
    54
    Completed
    47
    52
    53
    51
    Not completed
    6
    0
    3
    3
         Pretreatment Event/Adverse Event
    1
    -
    1
    -
         Major Protocol Deviation
    1
    -
    -
    1
         Voluntary Withdrawal
    2
    -
    2
    2
         Lost to follow-up
    1
    -
    -
    -
         Reason not Specified
    1
    -
    -
    -
    Period 2
    Period 2 title
    Withdrawal Phase (From Weeks 6 to 8)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 WD Phase: Pooled Placebo
    Arm description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive placebo in WD Phase, orally, once daily from Week 6-8. Pooled placebo included all participants who were on AZM or losartan in DB period and switched to placebo in WD Phase.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablet, orally

    Arm title
    		 WD Phase: Losartan 100 mg + 50 mg
    Arm description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive losartan in WD Phase. Participants with body weight >=25 to <50 kg received losartan 50 mg orally, once daily from Weeks 6-8 or participants with body weight >=50 kg received losartan 100 mg orally, once daily from Weeks 6-8 in WD Phase.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Losartan potassium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Losartan over encapsulated tablets, 50 mg, orally

    Investigational medicinal product name
    Losartan potassium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Losartan over encapsulated tablets, 100 mg, orally

    Arm title
    		 WD Phase: AZM-L 10 mg
    Arm description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to AZM-L in WD Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-L 10 mg orally, once daily from Weeks 6-8 in WD Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 10 mg, orally

    Arm title
    		 WD Phase: AZM-M 20 mg
    Arm description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive AZM-M in WB Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-M 20 mg orally, once daily from Weeks 6-8 WD Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 20 mg, orally

    Arm title
    		 WD Phase: AZM-H 40 mg + 80 mg
    Arm description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive AZM-H in WD Phase. Participants with body weight >=25 to <50 kg received AZM-M 40 mg orally, once daily from Weeks 6-8 or participants with body weight >=50 kg received AZM-M 80 mg orally, once daily from Weeks 6-8 in WD Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 40 mg, orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 80 mg, orally

    Number of subjects in period 2
    		WD Phase: Pooled Placebo WD Phase: Losartan 100 mg + 50 mg WD Phase: AZM-L 10 mg WD Phase: AZM-M 20 mg WD Phase: AZM-H 40 mg + 80 mg
    Started
    103
    23
    26
    26
    25
    Completed
    103
    23
    26
    25
    25
    Not completed
    0
    0
    0
    1
    0
         Consent withdrawn by subject
    -
    -
    -
    1
    -
    Period 3
    Period 3 title
    Open-Label Phase (From Weeks 8 to 52)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OL Phase: AZM Only 10 mg + 20 mg + 40 mg/ 80 mg
    Arm description
    		 Following the WD Phase, participants who had primary and secondary hypertension were randomized to AZM only Open-label Phase. Participants with body weight >=25 to <50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 20 or 40 mg from Weeks 12-52 or Participants with body weight >=50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 10, 20, 40, or 80 mg AZM orally, once daily from Weeks 12-52 in Open-label Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 10 mg orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 20 mg orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 40 mg orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 80 mg orally

    Arm title
    		 OL Phase: AZM Plus [AZM + Other Antihypertensives]
    Arm description
    		 Following the WD Phase, participants who had primary and secondary hypertension were randomized to AZM Plus in Open-label Phase. Participants with body weight >=25 to <50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 10, 20, or 40 mg AZM orally, once daily from Weeks 12-52 or body weight ≥50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 10, 20, 40, or 80 mg AZM orally, once daily from Weeks 12-52 plus other antihypertensive medications as needed according to a titrate-to-target algorithm, antihypertensive medication in Open-label Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 10 mg orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 40 mg orally

    Investigational medicinal product name
    Azilsartan Medoxomil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    AZM tablets, 80 mg orally

    Investigational medicinal product name
    Antihypertensive Agents (a calcium channel blocker - amlodipine; a diuretic - hydrochlorothiazide, or a beta-blocker -metoprolol)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Antihypertensive tablet, orally

    Number of subjects in period 3 [1]
    		OL Phase: AZM Only 10 mg + 20 mg + 40 mg/ 80 mg OL Phase: AZM Plus [AZM + Other Antihypertensives]
    Started
    156
    41
    Completed
    140
    41
    Not completed
    16
    0
         Consent withdrawn by subject
    7
    -
         Study Termination
    1
    -
         Pregnancy
    1
    -
         Lost to follow-up
    2
    -
         Reason not Specified
    5
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all participants who completed previous period, entered the preceding period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DB Phase: Losartan 25 mg + 50 mg + 100 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the losartan in the DB Phase. Participants with body weight >=25 to <50 kg were randomized to receive losartan 25 mg orally once daily, from Weeks 0 to 2 and losartan 50 mg from Weeks 2 to 6 and participants with body weight >=50 kg received losartan orally once daily 50 mg, from Weeks 0 to 2 and losartan 100 mg from Weeks 2 to 6 in the DB Phase.

    Reporting group title
    DB Phase: Low-Dose Azilsartan Medoxomil (AZM-L) 10 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the low-dose AZM-L DB Phase. Participants with body weight >= 25 to <50 kg or >= 50 kg received AZM-L 10 mg, orally, once daily from Week 0-6 in the DB Phase.

    Reporting group title
    DB Phase: AZM-M 10 mg+20 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive Intermediate-Dose Azilsartan Medoxomil (AZM-M) in the DB Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-M orally, once daily 10 mg from Weeks 0-2 and AZM-M 20 mg from Weeks 2-6 in the DB Phase.

    Reporting group title
    DB Phase: AZM-H 10 mg + 40 mg/ 80 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive High-Dose Azilsartan Medoxomil (AZM-H) in the DB Phase. Participants with body weight >=25 to <50 kg received AZM-H orally, once daily 10 mg from Weeks 0-2 and AZM-H 40 mg from Weeks 2-6 and participants with body weight >=50 kg received AZM-H orally, once daily 10 mg from Weeks 0-2 and AZM-H 80 mg from Weeks 2-6 in the DB Phase.

    Reporting group values
    		 DB Phase: Losartan 25 mg + 50 mg + 100 mg DB Phase: Low-Dose Azilsartan Medoxomil (AZM-L) 10 mg DB Phase: AZM-M 10 mg+20 mg DB Phase: AZM-H 10 mg + 40 mg/ 80 mg Total
    Number of subjects
    		 53 52 56 54 215
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 13.2 ( 3.18 ) 13.4 ( 2.92 ) 13.4 ( 3.10 ) 13.5 ( 2.85 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 25 28 16 25 94
        Male
    		 28 24 40 29 121
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 17 13 12 8 50
        Non-Hispanic or Latino
    		 36 39 44 46 165
    Race
    Units: Subjects
        American Indian or Alaskan Native
    		 1 1 0 1 3
        Black or African American
    		 13 13 14 15 55
        White
    		 38 38 42 37 155
        Multiracial
    		 1 0 0 1 2
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 159.4 ( 15.51 ) 159.0 ( 15.11 ) 160.3 ( 17.43 ) 158.9 ( 14.67 ) -
    Body Mass Index (BMI)
    BMI=weight (kg)/[height (m)^2]
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 26.35 ( 7.466 ) 27.98 ( 8.360 ) 25.41 ( 6.977 ) 26.75 ( 7.309 ) -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 69.00 ( 26.235 ) 72.53 ( 28.556 ) 66.65 ( 24.627 ) 68.94 ( 24.744 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    DB Phase: Losartan 25 mg + 50 mg + 100 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the losartan in the DB Phase. Participants with body weight >=25 to <50 kg were randomized to receive losartan 25 mg orally once daily, from Weeks 0 to 2 and losartan 50 mg from Weeks 2 to 6 and participants with body weight >=50 kg received losartan orally once daily 50 mg, from Weeks 0 to 2 and losartan 100 mg from Weeks 2 to 6 in the DB Phase.

    Reporting group title
    DB Phase: Low-Dose Azilsartan Medoxomil (AZM-L) 10 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the low-dose AZM-L DB Phase. Participants with body weight >= 25 to <50 kg or >= 50 kg received AZM-L 10 mg, orally, once daily from Week 0-6 in the DB Phase.

    Reporting group title
    DB Phase: AZM-M 10 mg+20 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive Intermediate-Dose Azilsartan Medoxomil (AZM-M) in the DB Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-M orally, once daily 10 mg from Weeks 0-2 and AZM-M 20 mg from Weeks 2-6 in the DB Phase.

    Reporting group title
    DB Phase: AZM-H 10 mg + 40 mg/ 80 mg
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive High-Dose Azilsartan Medoxomil (AZM-H) in the DB Phase. Participants with body weight >=25 to <50 kg received AZM-H orally, once daily 10 mg from Weeks 0-2 and AZM-H 40 mg from Weeks 2-6 and participants with body weight >=50 kg received AZM-H orally, once daily 10 mg from Weeks 0-2 and AZM-H 80 mg from Weeks 2-6 in the DB Phase.
    Reporting group title
    WD Phase: Pooled Placebo
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive placebo in WD Phase, orally, once daily from Week 6-8. Pooled placebo included all participants who were on AZM or losartan in DB period and switched to placebo in WD Phase.

    Reporting group title
    WD Phase: Losartan 100 mg + 50 mg
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive losartan in WD Phase. Participants with body weight >=25 to <50 kg received losartan 50 mg orally, once daily from Weeks 6-8 or participants with body weight >=50 kg received losartan 100 mg orally, once daily from Weeks 6-8 in WD Phase.

    Reporting group title
    WD Phase: AZM-L 10 mg
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to AZM-L in WD Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-L 10 mg orally, once daily from Weeks 6-8 in WD Phase.

    Reporting group title
    WD Phase: AZM-M 20 mg
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive AZM-M in WB Phase. Participants with body weight >=25 to <50 kg or >=50 kg received AZM-M 20 mg orally, once daily from Weeks 6-8 WD Phase.

    Reporting group title
    WD Phase: AZM-H 40 mg + 80 mg
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive AZM-H in WD Phase. Participants with body weight >=25 to <50 kg received AZM-M 40 mg orally, once daily from Weeks 6-8 or participants with body weight >=50 kg received AZM-M 80 mg orally, once daily from Weeks 6-8 in WD Phase.
    Reporting group title
    OL Phase: AZM Only 10 mg + 20 mg + 40 mg/ 80 mg
    Reporting group description
    		 Following the WD Phase, participants who had primary and secondary hypertension were randomized to AZM only Open-label Phase. Participants with body weight >=25 to <50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 20 or 40 mg from Weeks 12-52 or Participants with body weight >=50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 10, 20, 40, or 80 mg AZM orally, once daily from Weeks 12-52 in Open-label Phase.

    Reporting group title
    OL Phase: AZM Plus [AZM + Other Antihypertensives]
    Reporting group description
    		 Following the WD Phase, participants who had primary and secondary hypertension were randomized to AZM Plus in Open-label Phase. Participants with body weight >=25 to <50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 10, 20, or 40 mg AZM orally, once daily from Weeks 12-52 or body weight ≥50 kg received AZM 10 mg orally, once daily from Weeks 8-12 and 10, 20, 40, or 80 mg AZM orally, once daily from Weeks 12-52 plus other antihypertensive medications as needed according to a titrate-to-target algorithm, antihypertensive medication in Open-label Phase.

    Subject analysis set title
    WD Phase: Pooled AZM
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive AZM in WD Phase. Participants received AZM-L 10 mg, AZM – M 20 mg, and AZM – H 40 mg/80 mg orally, once daily from Weeks 6-8 based on their body weight. Data for all participants were pooled for analysis and is reported together in this arm.

    Subject analysis set title
    DB Phase: Pooled AZM
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the AZM in the DB phase. Participants received AZM-L 10 mg from Week 0-6, AZM-M and AZM-L 10 mg from Weeks 0-2, AZM-M 20 mg, and AZM-H 40 mg/80 mg from Weeks 2-6 orally, once daily based on their body weight. Data for all participants were pooled for analysis and is reported together in this arm.

    Subject analysis set title
    OL Phase: Pooled AZM‌
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Following the WD Phase, participants who had primary and secondary hypertension were randomized to receive AZM in Open-label Phase. Participants received AZM-L 10 mg from Weeks 8-12, AZM-M and AZM-L 10 mg, AZM-M 20 mg, and AZM-H 40 mg/80 mg from Weeks 12-52 orally, once daily based on their body weight. Data for all participants were pooled for analysis and is reported together in this arm.

    Primary: Change From Week 6 (Final Visit) of the Double-Blind Phase to Week 8 (Final Visit) of the Withdrawal Phase in Trough Clinic Seated Diastolic Blood Pressure (SeDBP)

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    End point title
    		 Change From Week 6 (Final Visit) of the Double-Blind Phase to Week 8 (Final Visit) of the Withdrawal Phase in Trough Clinic Seated Diastolic Blood Pressure (SeDBP)
    End point description
    The change in trough clinic seDBP measured From Week 6 (Final Visit) of the DB Phase to Week 8 (Final Visit) of the WD Phase. The trough is the average of the non-missing values of 3 serial trough sitting DBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 to Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. The primary endpoint compared the change in SeDBP in Pooled AZM versus Pooled Placebo arm. Full Analysis Set included all randomized participants who had received at least one dose of double-blind study medication for the respective study phase. ‘n’ indicates the number of participants with data available at the given time-point.
    End point type
    Primary
    End point timeframe
    Week 6 (Final Visit) of the DB phase to Week 8 (Final Visit) of the WD phase
    End point values
    		 WD Phase: Pooled Placebo WD Phase: Pooled AZM
    Number of subjects analysed
    79
    77
    Units: millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        Week 6 (n= 79,77)
    74.2 ( 8.43 )
    74.6 ( 8.77 )
        Change From Weeks 6 to 8 (n= 79,76)
    3.9 ( 8.00 )
    -1.6 ( 6.69 )
    Statistical analysis title
    		 Pooled AZM vs Pooled Placebo
    Comparison groups
    WD Phase: Pooled Placebo v WD Phase: Pooled AZM
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [1]
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares (LS) Mean Difference
    Point estimate
    -5.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.29
         upper limit
    		 -3.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.956
    Notes
    [1] - Comparisons between pooled AZM dose to pooled placebo were done from framework of analysis of covariance (ANCOVA) using contrast statements from within sequential testing procedure of successful conclusion of statistical significance.

    Secondary: Change From Week 6 (Final Visit) of the Double-Blind Phase to Week 8 (Final Visit) of the Withdrawal Phase in Trough Clinic Seated Systolic Blood Pressure (SeSBP)

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    End point title
    		 Change From Week 6 (Final Visit) of the Double-Blind Phase to Week 8 (Final Visit) of the Withdrawal Phase in Trough Clinic Seated Systolic Blood Pressure (SeSBP)
    End point description
    The change in trough clinic seSBP measured From Week 6 (Final Visit) of the DB Phase to Week 8 (Final Visit) of the WD Phase. The trough is the average of the non-missing values of 3 serial trough seSBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 to Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. This secondary endpoint compared the change in Trough SeSBP in Pooled AZM versus Pooled Placebo arm. FAS included all randomized participants who had received at least one dose of double-blind study medication for the respective study phase. ‘n’ indicates the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Week 6 (Final Visit) of the DB phase to Week 8 (Final Visit) of the WD
    End point values
    		 WD Phase: Pooled Placebo WD Phase: Pooled AZM
    Number of subjects analysed
    79
    77
    Units: mmHg
    arithmetic mean (standard deviation)
        Week 6 (n=79, 77)
    122.5 ( 13.65 )
    122.2 ( 13.18 )
        Change from Weeks 6 to 8 (n=79, 76)
    4.4 ( 9.96 )
    -2.3 ( 8.72 )
    Statistical analysis title
    		 Pooled AZM Vs Pooled Placebo
    Comparison groups
    WD Phase: Pooled Placebo v WD Phase: Pooled AZM
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -7.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.67
         upper limit
    		 -4.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.34
    Notes
    [2] - Comparisons between Pooled AZM dose to Pooled Placebo were done from the framework of the above ANCOVA using contrast statements. The p-value indicates significance at the 5% level.

    Secondary: Change From Week 6 (Final Visit) of the Double-Blind Phase to Week 8 (Final Visit) of the Withdrawal Phase in Mean Arterial Pressure (MAP)

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    End point title
    		 Change From Week 6 (Final Visit) of the Double-Blind Phase to Week 8 (Final Visit) of the Withdrawal Phase in Mean Arterial Pressure (MAP)
    End point description
    MAP was calculated using formula: MAP= seSBP +2 (seDBP)/3. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 to Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. This secondary endpoint compared the MAP in pooled AZM versus pooled placebo. FAS included all randomized participants who had received at least one dose of double-blind study medication for the respective study phase. ‘n’ indicates the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Week 6 (Final Visit) of the DB Phase to Week 8 (Final Visit) of the WD Phase
    End point values
    		 WD Phase: Pooled Placebo WD Phase: Pooled AZM
    Number of subjects analysed
    79
    77
    Units: mmHg
    arithmetic mean (standard deviation)
        Week 6 (n=79, 77)
    90.3 ( 9.25 )
    90.5 ( 9.41 )
        Change from Weeks 6 to 8 (n=79, 76)
    4.1 ( 7.43 )
    -1.8 ( 6.63 )
    Statistical analysis title
    		 Pooled AZM Vs Pooled Placebo
    Comparison groups
    WD Phase: Pooled Placebo v WD Phase: Pooled AZM
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [3]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -5.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.86
         upper limit
    		 -4.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.957
    Notes
    [3] - Comparisons between Pooled AZM dose to Pooled Placebo were done from framework of ANCOVA using contrast statements from within sequential testing procedure of successful statistical significance. P-value indicates significance at 5% level.

    Secondary: Change From Baseline in Trough Clinic seDBP at Week 6 (Final Visit)

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    End point title
    		 Change From Baseline in Trough Clinic seDBP at Week 6 (Final Visit) [4]
    End point description
    The change in trough clinic seDBP measured at Week 6 relative to Baseline. The trough is the average of the non-missing value of serial trough seDBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 blood pressure was measured approximately 24 hours after the previous day's dose. This secondary endpoint compared the seDBP at Week 6 in pooled AZM versus losartan. FAS included all randomized participants who had received at least one dose of DB study medication for the respective study phase. ‘n’ indicates the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 6 (Final Visit) of the DB Phase
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data was reported for the pooled analyses in all the endpoints.
    End point values
    		 DB Phase: Losartan 25 mg + 50 mg + 100 mg DB Phase: Pooled AZM
    Number of subjects analysed
    53
    162
    Units: mmHg
    arithmetic mean (standard deviation)
        Baseline (n=53, 162)
    87.6 ( 6.93 )
    85.9 ( 5.68 )
        Change from Baseline to Week 6 (n=47, 156)
    -9.5 ( 8.10 )
    -11.6 ( 8.71 )
    Statistical analysis title
    		 Pooled AZM vs Losartan
    Comparison groups
    DB Phase: Losartan 25 mg + 50 mg + 100 mg v DB Phase: Pooled AZM
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012 [5]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -3.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.17
         upper limit
    		 -0.78
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.366
    Notes
    [5] - Comparisons between each AZM dose to losartan were done from the framework of the above MMRM. The p-value indicates significance at the 5% level.

    Secondary: Change From Baseline in Trough Clinic seSBP at Week 6 (Final Visit)

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    End point title
    		 Change From Baseline in Trough Clinic seSBP at Week 6 (Final Visit) [6]
    End point description
    The change in trough clinic seSBP measured at Week 6 relative to Baseline. The trough is the average of the non-missing values of serial trough seSBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 blood pressure was measured approximately 24 hours after the previous day's dose. This secondary endpoint compared the seSBP in pooled AZM versus losartan. FAS included all randomized participants who had received at least one dose of DB study medication for the respective study phase. ‘n’ indicates the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 6 (Final Visit) of the DB Phase
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data was reported for the pooled analyses in all the endpoints.
    End point values
    		 DB Phase: Losartan 25 mg + 50 mg + 100 mg DB Phase: Pooled AZM
    Number of subjects analysed
    53
    162
    Units: mmHg
    arithmetic mean (standard deviation)
        Baseline (n=53, 162)
    134.3 ( 9.68 )
    132.3 ( 10.42 )
        Change from Baseline to Week 6 (n=47, 156)
    -10.0 ( 11.57 )
    -10.0 ( 9.48 )
    Statistical analysis title
    		 Pooled AZM Vs Losartan
    Comparison groups
    DB Phase: Losartan 25 mg + 50 mg + 100 mg v DB Phase: Pooled AZM
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.547 [7]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.23
         upper limit
    		 2.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.642
    Notes
    [7] - Comparisons between each AZM dose to losartan were done from the framework of the above MMRM.

    Secondary: Change From Baseline in Trough Clinic MAP at Week 6 (Final Visit)

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    End point title
    		 Change From Baseline in Trough Clinic MAP at Week 6 (Final Visit) [8]
    End point description
    The change in trough clinic MAP measured at Week 6 relative to Baseline. The trough is the average of the non-missing value of serial trough MAP measurements. MAP was calculated using formula: MAP= seSBP +2 (seDBP)/3. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. MAP was measured approximately 24 hours after the previous day's dose. This secondary endpoint compared the MAP in pooled AZM versus Losartan.Full Analysis Set included all randomized participants who had received at least one dose of DB study medication for the respective study phase. ‘n’ indicates the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 6 (Final Visit) of the DB phase
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data was reported for the pooled analyses in all the endpoints.
    End point values
    		 DB Phase: Losartan 25 mg + 50 mg + 100 mg DB Phase: Pooled AZM
    Number of subjects analysed
    53
    162
    Units: mmHg
    arithmetic mean (standard deviation)
        Baseline (n=53, 162)
    103.1 ( 7.19 )
    101.4 ( 6.41 )
        Change from Baseline to Week 6 (47, 156)
    -9.6 ( 8.66 )
    -11.1 ( 7.93 )
    Statistical analysis title
    		 Pooled AZM Vs Losartan
    Comparison groups
    DB Phase: Losartan 25 mg + 50 mg + 100 mg v DB Phase: Pooled AZM
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.062 [9]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -2.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.15
         upper limit
    		 0.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.337
    Notes
    [9] - Comparisons between each AZM dose to losartan were done from the framework of the above MMRM.

    Secondary: Percentage of Participants who Achieved Target Blood Pressure (BP) (SeDBP, SeSBP, both) at Week 8 (Final Visit) of the Withdrawal Phase, With the Target Defined as <90th Percentile for Age, Gender, and Height

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    End point title
    		 Percentage of Participants who Achieved Target Blood Pressure (BP) (SeDBP, SeSBP, both) at Week 8 (Final Visit) of the Withdrawal Phase, With the Target Defined as <90th Percentile for Age, Gender, and Height
    End point description
    Clinic seDBP, seSBP both (seDBP, and seSBP) target defined as <90th Percentile for age, gender, and height. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose. This secondary endpoint compared the SeDBP, SeSBP, both in pooled AZM versus pooled placebo. Full Analysis Set included all randomized participants who had received at least one dose of DB study medication for the respective study phase. The analysis was based on last observation carried forward (LOCF).
    End point type
    Secondary
    End point timeframe
    Week 8 (Final Visit) of the WD Phase
    End point values
    		 WD Phase: Pooled Placebo WD Phase: Pooled AZM
    Number of subjects analysed
    79
    77
    Units: percentage of participants
    number (not applicable)
        Achieved Target seDBP
    50.6
    66.2
        Achieved Target seSBP
    39.2
    61.0
        Achieved Both (Target seDBP and seSBP)
    30.4
    54.5
    Statistical analysis title
    		 SeDBP: Pooled AZM vs Pooled Placebo
    Comparison groups
    WD Phase: Pooled Placebo v WD Phase: Pooled AZM
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.028 [10]
    Method
    		 Logistic Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.09
         upper limit
    		 4.43
    Notes
    [10] - The p-values and odds ratios were obtained using a logistic model with treatment, age, race, and weight as fixed effects and corresponding baseline clinic BP as a covariate. The p-value indicated significance at the 5% level.
    Statistical analysis title
    		 SeSBP: Pooled AZM Vs Pooled Placebo
    Comparison groups
    WD Phase: Pooled Placebo v WD Phase: Pooled AZM
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.016 [11]
    Method
    		 Logistic Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 4.76
    Notes
    [11] - The p-values and odds ratios were obtained using a logistic model with treatment, age, race, and weight as fixed effects and corresponding baseline clinic BP as a covariate.
    Statistical analysis title
    		 Both: Pooled AZM Vs Pooled Placebo
    Comparison groups
    WD Phase: Pooled Placebo v WD Phase: Pooled AZM
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005 [12]
    Method
    		 Logistic Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.36
         upper limit
    		 5.77
    Notes
    [12] - The p-values and odds ratios were obtained using a logistic model with treatment, age, race, and weight as fixed effects and corresponding baseline clinic BP as a covariate. The p-value indicated significance at the 1% level.

    Secondary: Percentage of Participants with At least One Treatment-Emergent Adverse Event (TEAE)

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    End point title
    		 Percentage of Participants with At least One Treatment-Emergent Adverse Event (TEAE) [13]
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation subject administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. TEAE is defined as any AE that started or worsened on or after the start of the study medication and after the discontinuation of the study medication.
    End point type
    Secondary
    End point timeframe
    From the time of the first dose of study drug through 30 days after the last dose (Up to 54 weeks)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data was reported for the pooled analyses in all the endpoints.
    End point values
    		 DB Phase: Losartan 25 mg + 50 mg + 100 mg WD Phase: Pooled Placebo WD Phase: Losartan 100 mg + 50 mg WD Phase: Pooled AZM DB Phase: Pooled AZM OL Phase: Pooled AZM‌
    Number of subjects analysed
    53
    103
    23
    77
    162
    197
    Units: percentage of participants
        number (not applicable)
    32.1
    12.6
    8.7
    15.6
    33.3
    43.1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the time of the first dose of study drug through 30 days after the last dose (Up to 54 weeks)
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Data for adverse events are reported for each phase of the study
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    OL Phase: Pooled AZM
    Reporting group description
    		 Following the WD Phase, participants who had primary and secondary hypertension were randomized to receive AZM in Open-label Phase. Participants received AZM-L 10 mg from Week 8-12, AZM-M and AZM-L 10 mg, AZM-M 20 mg, and AZM-H 40 mg/ 80 mg from Week 12-52 orally, once daily based on their body weight. Data for all participants were pooled for analysis and is reported together in this arm.

    Reporting group title
    DB Phase: Pooled AZM
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the AZM in the DB phase. Participants received AZM-L 10 mg from Week 0-6, AZM-M and AZM-L 10 mg from Week 0-2, AZM-M 20 mg, and AZM-H 40 mg/ 80 mg from Week 2-6 orally, once daily based on their body weight. Data for all participants were pooled for analysis and is reported together in this arm.

    Reporting group title
    WD Phase: Pooled Placebo
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive placebo in WD Phase, orally, once daily from Week 6-8. Pooled placebo included all participants who were on AZM or losartan in DB period and switched to placebo in WD Phase.

    Reporting group title
    WD Phase: Losartan
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive losartan in WD Phase. Participants with body weight >=25 to <50 kg received losartan 50 mg orally, once daily from Weeks 6-8 or participants with body weight >=50 kg received losartan 100 mg orally, once daily from Weeks 6-8 in WD Phase.

    Reporting group title
    DB Phase: Losartan
    Reporting group description
    		 Following the Placebo Run-in Period, participants who had primary or secondary hypertension were randomized to receive the losartan in the DB Phase. Participants with body weight >=25 to <50 kg were randomized to receive losartan 25 mg orally once daily, from Weeks 0 to 2 and losartan 50 mg from Weeks 2 to 6 and participants with body weight >=50 kg received losartan orally once daily 50 mg, from Weeks 0 to 2 and losartan 100 mg from Weeks 2 to 6 in the DB Phase.

    Reporting group title
    WD Phase: Pooled AZM
    Reporting group description
    		 Following the DB Phase, participants who had primary or secondary hypertension were randomized to receive AZM in WD Phase. Participants received AZM-L 10 mg, AZM – M 20 mg, and AZM – H 40 mg/ 80 mg orally, once daily from Week 6-8 based on their body weight. Data for all participants were pooled for analysis and is reported together in this arm.

    Serious adverse events
    		 OL Phase: Pooled AZM DB Phase: Pooled AZM WD Phase: Pooled Placebo WD Phase: Losartan DB Phase: Losartan WD Phase: Pooled AZM
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 197 (4.57%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    2 / 53 (3.77%)
    1 / 77 (1.30%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    Blood pressure increased
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Loss of consciousness
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Autism spectrum disorder
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Pneumonia
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Peritonitis
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 OL Phase: Pooled AZM DB Phase: Pooled AZM WD Phase: Pooled Placebo WD Phase: Losartan DB Phase: Losartan WD Phase: Pooled AZM
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    84 / 197 (42.64%)
    53 / 162 (32.72%)
    13 / 103 (12.62%)
    2 / 23 (8.70%)
    15 / 53 (28.30%)
    11 / 77 (14.29%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    2 / 197 (1.02%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    4 / 197 (2.03%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    4
    1
    0
    0
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Vaginal discharge
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Polycystic ovaries
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Bronchospasm
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Cough
         subjects affected / exposed
    3 / 197 (1.52%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    4 / 197 (2.03%)
    0 / 162 (0.00%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    4
    0
    1
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    6 / 197 (3.05%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    6
    1
    0
    0
    0
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    2 / 197 (1.02%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Nervousness
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    Arthroscopy
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 197 (1.02%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    2
    2
    0
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 197 (0.51%)
    3 / 162 (1.85%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    2 / 197 (1.02%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    Cardiac murmur
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Blood glucose decreased
         subjects affected / exposed
    0 / 197 (0.00%)
    2 / 162 (1.23%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Weight increased
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Influenza B virus test positive
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Ligament injury
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Joint dislocation
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Fibula fracture
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Upper limb fracture
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Soft tissue injury
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Tooth fracture
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 197 (2.03%)
    5 / 162 (3.09%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    4
    5
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    17 / 197 (8.63%)
    8 / 162 (4.94%)
    6 / 103 (5.83%)
    0 / 23 (0.00%)
    3 / 53 (5.66%)
    3 / 77 (3.90%)
         occurrences all number
    17
    8
    6
    0
    3
    3
    Hypoaesthesia
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 197 (0.00%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    Neutropenia
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Lymphadenitis
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Middle ear inflammation
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Ear pain
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Conjunctivitis allergic
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    7 / 197 (3.55%)
    1 / 162 (0.62%)
    2 / 103 (1.94%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    7
    1
    2
    0
    0
    0
    Enteritis
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    8 / 197 (4.06%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    2 / 53 (3.77%)
    0 / 77 (0.00%)
         occurrences all number
    8
    1
    0
    0
    2
    0
    Constipation
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    4 / 197 (2.03%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    4
    1
    0
    0
    0
    0
    Odynophagia
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Paraesthesia oral
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Salivary gland pain
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    6 / 197 (3.05%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    6
    0
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Food poisoning
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Frequent bowel movements
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    2 / 197 (1.02%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    4 / 197 (2.03%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    1 / 77 (1.30%)
         occurrences all number
    4
    2
    0
    0
    1
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Acne
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Nail bed inflammation
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 197 (0.00%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Rash
         subjects affected / exposed
    2 / 197 (1.02%)
    1 / 162 (0.62%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    0
    Pruritus allergic
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Thyroid cyst
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    2 / 197 (1.02%)
    4 / 162 (2.47%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    4
    1
    0
    0
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    3 / 197 (1.52%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    3
    1
    0
    0
    0
    1
    Myositis
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 197 (0.51%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    Bacteraemia
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    3 / 197 (1.52%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    Cystitis
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Dental fistula
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dermatophytosis
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Gastrointestinal viral infection
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    1 / 23 (4.35%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    Gastroenteritis
         subjects affected / exposed
    5 / 197 (2.54%)
    4 / 162 (2.47%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    5
    4
    1
    0
    0
    0
    Herpangina
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Laryngitis
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    4 / 197 (2.03%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    8 / 197 (4.06%)
    5 / 162 (3.09%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    3 / 53 (5.66%)
    0 / 77 (0.00%)
         occurrences all number
    8
    5
    1
    0
    3
    0
    Otitis externa
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Otitis media acute
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    7 / 197 (3.55%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    7
    1
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    1 / 103 (0.97%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    Pharyngotonsillitis
         subjects affected / exposed
    3 / 197 (1.52%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    3
    1
    0
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    2 / 197 (1.02%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    Viral pharyngitis
         subjects affected / exposed
    2 / 197 (1.02%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    3
    0
    0
    0
    0
    1
    Tonsillitis
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Appendicitis
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 197 (4.06%)
    8 / 162 (4.94%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    2 / 77 (2.60%)
         occurrences all number
    8
    8
    0
    0
    0
    2
    Tracheobronchitis
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Viral infection
         subjects affected / exposed
    5 / 197 (2.54%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    5
    1
    0
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 197 (0.51%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    1 / 23 (4.35%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    1
    1
    0
    1
    1
    0
    Varicella
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    3 / 197 (1.52%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Dyslipidaemia
         subjects affected / exposed
    0 / 197 (0.00%)
    1 / 162 (0.62%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Obesity
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 197 (0.00%)
    2 / 162 (1.23%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    1 / 53 (1.89%)
    0 / 77 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    Insulin resistance
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lipid metabolism disorder
         subjects affected / exposed
    1 / 197 (0.51%)
    0 / 162 (0.00%)
    0 / 103 (0.00%)
    0 / 23 (0.00%)
    0 / 53 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Dec 2018
    The amendment included following: - Primary change was related to the sample size justification. Upon review of the pooled blinded data of the primary endpoint, the SD for the primary endpoint (change from Week 6/Final Visit of the DB Phase to Week 8/Final Visit of the WD Phase in seDBP between AZM and placebo) was 7.82 mmHg which was much less than what had been previously specified. Given variability in the SD, an SD estimate of 8.3 mmHg was to be used in the revised sample size justification. Assuming an SD for the primary endpoint (change from Week 6/Final Visit of the DB Phase to Week 8/Final Visit of the WD Phase in seDBP between AZM and placebo) of 8.3 mmHg and an overall 10% dropout rate, 156 participants (78 pooled AZM versus 78 pooled Placebo) would provide >80% power to detect a difference of 4.5 mmHg between the pooled AZM group and placebo by a 2-sample t-test of the mean seDBP change from Week 6/Final Visit of the DB Phase to Week 8/Final Visit of the WD Phase at the 0.05 significance level (2-sided). Prior to the final protocol amendment, the approximate expected percentage of participant with secondary hypertension was to be between 40% to 60% and no more than approximately 25% of participants were to be post-renal transplant participants and no more than approximately 60% of participants were to weigh greater than or equal to 50 kg at Baseline.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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